Next Article in Journal
Phenotypic Heterogeneity of Cancer Associated Fibroblasts in Cervical Cancer Progression: FAP as a Central Activation Marker
Next Article in Special Issue
Unlocking Potential: A Comprehensive Overview of Cell Culture Banks and Their Impact on Biomedical Research
Previous Article in Journal
Transgene-Free Cynomolgus Monkey iPSCs Generated under Chemically Defined Conditions
Previous Article in Special Issue
Unlocking Translational Potential: Conditionally Reprogrammed Cells in Advancing Breast Cancer Research
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Cells
Volume 13
Issue 7
10.3390/cells13070559
cells-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Commentary

Nasopharyngeal Carcinoma Cell Lines: Reliable Alternatives to Primary Nasopharyngeal Cells?

by
Anna Makowska
1,* and
Ralf Weiskirchen
2,*
1
Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, RWTH University Hospital Aachen, D-52074 Aachen, Germany
2
Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, D-52074 Aachen, Germany
*
Authors to whom correspondence should be addressed.
Cells 2024, 13(7), 559; https://doi.org/10.3390/cells13070559
Submission received: 19 February 2024 / Revised: 17 March 2024 / Accepted: 20 March 2024 / Published: 22 March 2024
(This article belongs to the Special Issue Primary and Continued Cell Cultures)
Browse Figures
Review Reports Versions Notes

Abstract

:
Nasopharyngeal carcinoma (NPC) is a type of cancer that originates from the mucosal lining of the nasopharynx and can invade and spread. Although contemporary chemoradiotherapy effectively manages the disease locally, there are still challenges with locoregional recurrence and distant failure. Therefore, it is crucial to have a deeper understanding of the molecular basis of NPC cell movement in order to develop a more effective treatment and to improve patient survival rates. Cancer cell line models are invaluable in studying health and disease and it is not surprising that they play a critical role in NPC research. Consequently, scientists have established around 80 immortalized human NPC lines that are commonly used as in vitro models. However, over the years, it has been observed that many cell lines are misidentified or contaminated by other cells. This cross-contamination leads to the creation of false cell lines that no longer match the original donor. In this commentary, we discuss the impact of misidentified NPC cell lines on the scientific literature. We found 1159 articles from 2000 to 2023 that used NPC cell lines contaminated with HeLa cells. Alarmingly, the number of publications and citations using these contaminated cell lines continued to increase, even after information about the contamination was officially published. These articles were most commonly published in the fields of oncology, pharmacology, and experimental medicine research. These findings highlight the importance of science policy and support the need for journals to require authentication testing before publication.

1. Introduction

Nasopharyngeal carcinoma (NPC) is a cancer that originates from the mucosal lining of the nasopharynx and can spread to other parts of the body. This type of tumor is most commonly found in East and Southeast Asia, particularly in the southern regions of China [1]. In China, approximately 3 out of every 100,000 people are diagnosed with NPC each year, while globally the number is 1.5 out of 100,000. The male to female ratio is around two-to-five [2,3,4,5]. It was estimated that there were 80,008 deaths from NPC in 2020. By the year 2040, an increase in the annual number of NPC cases is expected, rising from 133,354 in 2020 to 179,476. The projected number of deaths is expected to increase from 80,008 to 113,851. This represents a 34.58% increase in cases and a 42.29% increase in deaths, compared to 2020 [5]. Possible causes of NPC include exposure to secondhand smoke, alcohol consumption, eating preserved foods, infection with the Epstein–Barr virus (EBV), and genetic variations in the host [6]. According to the World Health Organization (WHO), NPC is divided into keratinizing squamous cell carcinoma (WHO type I); differentiated, non-keratinizing carcinoma (WHO type II); and undifferentiated, non-keratinizing carcinoma (WHO type III) [7].
Despite advances in chemoradiotherapy, both the recurrence of the tumor in the local area and its spread to distant sites remain significant challenges [8]. It is estimated that 21.3% of patients with nonmetastatic NPC experience treatment failure, primarily due to distant metastasis, within five years of initial treatment [9]. Therefore, a better understanding of the molecular mechanisms underlying the movement of NPC cells is crucial for developing more effective treatment strategies and improving patient survival rates.
Cancer cell line models serve as an essential laboratory resource, simplifying the study of health and disease. The majority of cell-intrinsic, targeted therapeutics were discovered and developed using continuous cell lines. These cell lines can be passaged repeatedly, recover reliably from cryopreservation, and maintain many characteristics of their original cell type or tissue [10,11,12]. These benefits make continuous cell lines an efficient and popular model system for studying normal cellular processes and various disease conditions.
For our study, we conducted two separate searches on the PubMed database. Both searches took place on 7 March 2024. The first search, using the terms “nasopharyngeal carcinoma” and “cell line”, resulted in 3746 hits for the period from 1970 to 2024 (https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29; accessed on 7 March 2024). The second search used the terms “nasopharyngeal carcinoma” and “cell line” for each single year between 1979 and 2024 (Table 1).
This second search yielded 4365 hits for the same period as the first search. This indicates an increasing use of NPC cell line models over the years, as evidenced by the number of studies. For instance, there were 17 studies in 1985, 78 studies in 2005, and 270 studies in 2020 (Figure 1).
Furthermore, a search for “nasopharyngeal carcinoma cell” conducted on 15 February 2024 on the Cellosaurus database, which is widely recognized as an authoritative source for cell line information, resulted in 80 human NPC cell lines (Table 2).
Cell lines play a crucial role in research, but they are often misidentified or contaminated by other cells. This can result in the creation of incorrect cell lines that do not match the original donor and may come from a different donor or species. Contamination can occur early on, where the original cell line may have never existed independently, or later, where the original may still exist in other stocks but is contaminated in the tested sample. This issue impacts the authenticity of cell lines as cancer models. Even widely used cell lines may not accurately represent the tumor type they are intended to come from due to changes in cell line shape, growth, and gene expression. Neglecting this problem can lead to inaccurate and misleading research data [57].
In cancer research, cell lines serve as invaluable models for studying cancer progression, diagnostics, and treatment advancements. Although they may not perfectly mimic the original tumor, they generally exhibit similar characteristics. Low-passage cancer cell lines are preferred due to their closer resemblance to the original tumor. Prolonged culturing can alter genetic and molecular profiles, emphasizing the need to monitor passage numbers. Variations in proliferation, migration, gene expression, and drug sensitivity can be attributed to passage number differences. Additionally, passage number influences DNA methylation levels, metabolic profiles, and gene/protein expression in cancer cell lines. Researchers must carefully select the appropriate passage number to maintain the consistency and reliability of the results. To ensure dependability and replicability, scientists should actively track growth, migration, and gene/protein profiles at specific passage numbers [58]. Prolonged culture can lead to reduced or altered key functions, rendering cell lines unreliable models of their original source material [59].
For nearly half a century, sporadic reports of HeLa cell contamination in numerous mammalian cell lines have been documented [60,61,62,63]. The previously mentioned contaminated cell lines have short tandem repeat (STR) profiles that are either identical or highly similar to HeLa. STR profiling is the most popular method for detecting cell contamination (Table 3). This analysis determines a cell line’s DNA profile by counting the number of times a DNA sequence, known as an STR unit, appears at a specific chromosomal location. The chromosomal location refers to the specific area on a chromosome where the DNA strand is located [64]. This molecular genotyping technique is now available for both human and mouse cell lines. When used regularly in cell culture management, this technique, along with other methods, significantly improves the detection of cellular cross-contamination. This leads to more reproducible and scientifically meaningful research outcomes [65].
The American Tissue Culture Collection (ATCC) has established standard guidelines advocating for the use of at least eight STR loci in human cell line authentication. These recommended loci include TH01, TPOX, vWA, CSF1PO, D16S539, D7S820, D13S317, and D5S8181, along with the Amelogenin gene for gender identification [57,66]. These guidelines set the standards for authenticating cell lines. These STR loci play a crucial role in ensuring the quality and integrity of human cell lines, allowing researchers to demonstrate relatedness between cell lines and uniquely identify human cells. The adoption of these guidelines has facilitated broader cell line authentication testing in laboratories worldwide.
Table 3. Cell contamination detection methods.
Table 3. Cell contamination detection methods.
Detection MethodDescriptionReference
Isoenzyme analysisThe approach relies on the isoelectric separation of a distinct group of intracellular enzymes. These enzymes serve as markers, allowing differentiation between cell lines originating from humans, mice, or other mammals.[67]
HLA typingHLA typing, which uses serological methods and specific sera, identifies HLA antigens on cell surfaces. This complementary test helps detect cross-contamination within cell lines of the same species.[68]
DNA fingerprintingDNA fingerprinting relies on determining specific DNA sequences. Variable Number of Tandem Repeat (VNTR) and Short Tandem Repeat (STR) loci are amplified using PCR.[69]
The first instance of cross-contamination in NPC cell lines was reported in 2008 by Chan and his team, who discovered a significant degree of similarity between the STR profiles of two EBV-negative cell lines, CNE-1 and CNE-2 [31]. Additionally, they found that the STR profile of HeLa perfectly matched the STR profiles of CNE-1 and CNE-2 listed in the ATCC [31]. In 2015, Ye and his colleagues published a list of additional NPC cell lines contaminated with HeLa cells [54]. The recently released 12th version of the International Cell Line Authentication Committee (ICLAC) lists a total of eight NPC cell lines as being cross-contaminated (Table 4) [57].
All cell lines in this group carry the 13.3 allele at the STR locus D13S317, indicating that they are derived from HeLa, but also contain additional genetic material from an unidentified source. The true identities of the cell lines in this group remain uncertain. In addition, many other NPC cell lines listed in the Cellosaurus database (but not in the ICLAC register) are derived from the parental cells mentioned earlier, such as 13-9B (parental cell line SUNE), 5-8F/Erbitux (parental cell line 5-8F), CNE-2Z (parental cell line CNE-2), CNE1 SRPK1 KO, CNE1 SRPK1/2 KO, and CNE1 SRPK2 KO (all derived from parental cell line CNE-1), as well as CNE-IR (parental cell line CNE-2), HNE-2 (almost identical to HNE-1), HONE-1/CPT30 and HONE-1/CPT30R (parental cell line HONE-1), S18, S18-1C3, and S26 (parent cell line CNE-2). Considering all NPC cell lines mentioned earlier, it is reasonable to speculate that at least 25% of all NPC cells should be classified as misidentified.
Despite genetic profiling evidence showing that these cell lines are contaminated with HeLa cells, numerous research groups studying NPC have continued to use these cells, up until the present time. We conducted searches on the PubMed database from 2000 to 2023 to identify papers that used the HeLa-contaminated NPC cell lines listed in Table 3. Our search specifically targeted the improper use of these cell lines, which we defined as any description that was inaccurate or misleading when using the terms “nasopharyngeal carcinoma cell line”. We determined the incorrect usage of these cells based on the description provided, as these descriptions guide researchers in selecting cell lines for their studies. The search involved examining titles, abstracts, and the text of articles. Our study primarily focused on titles, abstracts, and methods sections, often without reference to the main text. Using this method, we identified a total of 1282 articles from 2000 to 2023 that utilized NPC cell lines contaminated with HeLa cells (Figure 2).
While the number of journals requiring authentication is increasing, only a few journal articles currently provide information on authentication testing. Researchers have no choice but to rely on the cell line data provided by the authors in order to determine the suitability of a cell line for their research. Although the tissue type or disease condition may not appear relevant to all studies, readers will use this information to select their own cell lines. Therefore, the information about cell lines must be accurate; otherwise, it can lead to misunderstandings within the research community when interpreting the results of that work. This issue becomes particularly crucial when cell line models are utilized for testing therapeutic agents [72].
A search conducted on the “Web of Science” database on 22 January 2024, using the terms “nasopharyngeal carcinoma” and “one of the eight HeLa contaminated cell lines”, reveals a growing trend in the use of misidentified NPC cell lines as models for NPC, over the years. Furthermore, the number of citations for these erroneous publications is also on the rise (as shown in Figure 3 and Table 5).
A concerning fact is that the number of publications and citations of misidentified NPC cell lines continued to increase even after the official announcement that NPC cell lines were contaminated with HeLa cell lines [31,54]. To better understand this issue, we examined information for the CNE2 cell line. This line is one of the most commonly used NPC cell lines identified as HeLa-contaminated. CNE2 is a poorly differentiated NPC epithelial cell line that originated from a primary tumor biopsy in China in 1983 [24]. Since most NPCs are poorly differentiated, the CNE2 cell line has been a crucial model for nasopharyngeal studies. A search on the “Web of Science” database using the terms “CNE2” and “nasopharyngeal carcinoma” yielded 416 articles focusing on the CNE2 cell line from 1983 to 2023. This cell line was identified as HeLa-contaminated in 2008 [31]. From 2008 to 2023, this cell line was mentioned in 361 articles. Furthermore, these articles were cited in an additional 5271 articles, including 132 articles with self-citations. Almost all articles did not provide an authentication test. For many decades, CNE2 has been a fundamental tool in various fields of biomedical research. Numerous grants have been allocated and significant progress has been made in understanding disease etiology and developing treatments and cures.
A search on the “Web of Science” database using the terms “CNE2” and “nasopharyngeal carcinoma” revealed the most prevalent research fields, including oncology, pharmacology, and experimental medical research. These fields were identified based on articles that focused on the CNE2 cell line from 2008 (the year it was discovered that CNE2 is contaminated with HeLa) to 2023 (as shown in Figure 4).
This search also brought attention to the global issue of using cells contaminated with HeLa. Assuming that approximately 10–12% of all NPC cell lines used worldwide are cross-contaminated, this suggests that potentially hundreds of millions of dollars spent in the biomedical and healthcare sectors globally may have been wasted on producing inaccurate or misleading data.
The examination of the eight NPC cell lines contaminated with HeLa presents a multifaceted scenario with various descriptions. Often, authors fail to acknowledge that NPC cells are actually variants of HeLa, even when they cite accurate sources that have reported this information. Furthermore, they tend to provide details about the source laboratory without including literature references that would help clarify the characteristics of the cells.
So far, improvements in citations have been lagging behind publishing changes, leading to a significant amount of incorrect data persisting in the research literature. Recent initiatives, such as standardizing cell line authentication [57], promoting consistent terminology [74], encouraging authentication in journals [75], establishing the International Cell Line Authentication Committee [76], and creating Cellosaurus, a cell line database [77], could help to increase the number of papers accurately citing NPCs.
Accurate cell line data and testing are crucial. However, even with authentication, cell lines may not accurately represent their original tissues or diseases due to factors such as source and reagent differences [78,79]. Therefore, the validity of a cell line as a research model, not only in the field of NPCs, should always be continually improved [80,81].

2. Conclusions

Improving the selection, cultivation conditions, and reporting practices of cell lines will enhance our preclinical research models. However, a significant concern arises if the volume of publications containing incorrect information about certain cell lines exceeds those with accurate data. This situation leads to the continued use of these erroneous cell lines in scientific research, despite their inaccuracies. They are still being referenced in the literature, which is a testament to the gravity of this issue. This problem is not just a fleeting one, but rather a persistent issue that could continue to plague the scientific community for the foreseeable future. The continued use of these incorrect cell lines could potentially skew research findings and conclusions. This is not a trivial matter as it could lead to a ripple effect of misinformation within the field. Misinformation can spread like wildfire, leading to a cascade of flawed research that builds upon the incorrect data. This could potentially result in wasted resources, misguided research directions, and, worst of all, incorrect scientific conclusions that could have far-reaching implications. Therefore, it is crucial to address this issue to ensure the integrity and reliability of future research. It is not just about correcting the current state of affairs, but also about setting up robust systems and practices to prevent such issues from recurring. This includes stringent verification processes, rigorous peer reviews, and fostering a culture of transparency and accountability in the scientific community. The routine use of STR profiling, isoenzyme analysis, HLA typing, DNA fingerprinting, or any other methods that allow for the detection of cross-contamination or misidentification of a cell line should be mandatory in all work with cell lines. By implementing these measures, we can safeguard the future of scientific research, ensuring that it remains a reliable source of knowledge and insight for humanity.

Author Contributions

Conceptualization, A.M. and R.W.; data curation, A.M. and R.W.; writing—original draft preparation, A.M. and R.W.; writing—review and editing, A.M. and R.W.; supervision, A.M. and R.W. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

This review only presents data that have been previously published. No new data were generated.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Chen, Y.P.; Chan, A.T.C.; Le, Q.T.; Blanchard, P.; Sun, Y.; Ma, J. Nasopharyngeal carcinoma. Lancet 2019, 394, 64–80. [Google Scholar] [CrossRef]
  2. Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018, 68, 394–424. [Google Scholar] [CrossRef]
  3. Chen, W.; Zheng, R.; Baade, P.D.; Zhang, S.; Zeng, H.; Bray, F.; Jemal, A.; Yu, X.Q.; He, J. Cancer statistics in China, 2015. CA Cancer J. Clin. 2016, 66, 115–132. [Google Scholar] [CrossRef]
  4. Ling, J.; Zhang, L.; Chang, A.; Huang, Y.; Ren, J.; Zhao, H.; Zhuo, X. Overexpression of KITLG predicts unfavorable clinical outcomes and promotes lymph node metastasis via the JAK/STAT pathway in nasopharyngeal carcinoma. Lab. Investig. 2022, 102, 1257–1267. [Google Scholar] [CrossRef] [PubMed]
  5. Zhang, Y.; Rumgay, H.; Li, M.; Cao, S.; Chen, W. Nasopharyngeal cancer incidence and mortality in 185 countries in 2020 and the projected burden in 2040: Population-based global epidemiological profiling. JMIR Public Health Surveill. 2023, 9, e49968. [Google Scholar] [CrossRef] [PubMed]
  6. Luo, H.; Yi, B. The role of exosomes in the pathogenesis of nasopharyngeal carcinoma and the involved clinical application. Int. J. Biol. Sci. 2021, 17, 2147–2156. [Google Scholar] [CrossRef] [PubMed]
  7. Li, Z.; Zong, Y.S. Review of the histological classification of nasopharyngeal carcinoma. J. Nasopharyng. Carcinoma 2014, 1, e15. [Google Scholar] [CrossRef]
  8. Nakanishi, Y.; Wakisaka, N.; Kondo, S.; Endo, K.; Sugimoto, H.; Hatano, M.; Ueno, T.; Ishikawa, K.; Yoshizaki, T. Progression of understanding for the role of Epstein-Barr virus and management of nasopharyngeal carcinoma. Cancer Metastasis Rev. 2017, 36, 435–447. [Google Scholar] [CrossRef]
  9. Sun, H.Q.; Kwiatkowska, K.; Wooten, D.C.; Yin, H.L. Effects of CapG overexpression on agonist-induced motility and second messenger generation. J. Cell Biol. 1995, 129, 147–156. [Google Scholar] [CrossRef] [PubMed]
  10. Wistuba, I.I.; Behrens, C.; Milchgrub, S.; Syed, S.; Ahmadian, M.; Virmani, A.K.; Kurvari, V.; Cunningham, T.H.; Ashfaq, R.; Minna, J.D.; et al. Comparison of features of human breast cancer cell lines and their corresponding tumors. Clin. Cancer Res. 1998, 4, 2931–2938. [Google Scholar]
  11. Ross, D.T.; Scherf, U.; Eisen, M.B.; Perou, C.M.; Rees, C.; Spellman, P.; Iyer, V.; Jeffrey, S.S.; Van de Rijn, M.; Waltham, M.; et al. Systematic variation in gene expression patterns in human cancer cell lines. Nat. Genet. 2000, 24, 227–235. [Google Scholar] [CrossRef]
  12. Capes-Davis, A.; Theodosopoulos, G.; Atkin, I.; Drexler, H.G.; Kohara, A.; MacLeod, R.A.; Masters, J.R.; Nakamura, Y.; Reid, Y.A.; Reddel, R.R.; et al. Check your cultures! A list of cross-contaminated or misidentified cell lines. Int. J. Cancer 2010, 127, 1–8. [Google Scholar] [CrossRef]
  13. Cellosaurus—A Knowledge Resource on Cell Lines. Available online: https://www.cellosaurus.org/ (accessed on 16 March 2024).
  14. Zhang, L.; Song, L.; Ma, Y.; Huang, B.; Liang, Q.; Zeng, Y. Differentially expressed gene in nasopharyngeal carcinoma cell lines with various metastatic potentialities. Zhonghua Zhong Liu Za Zhi 2002, 24, 430–434. [Google Scholar]
  15. Furukawa, M.; Umeda, R.; Hatano, M. Transfer of EBV (Epstein-Barr virus) genome from lymphoblastoid cells to established epithelial cells derived from human tissues Experimental studies on the viral etiology of nasopharyngeal carcinoma (NPC) related to EBV infection. Kanazawa Daigaku Juzen Igakkai Zasshi 1975, 84, 190–210. [Google Scholar]
  16. Zuo, Q.; Luo, R.C. Relationship between the insulin-like growth factor 1 receptor signaling pathway and the resistance of nasopharyngeal carcinoma to cetuximab. Zhonghua Zhong Liu Za Zhi 2010, 32, 575–579. [Google Scholar] [PubMed]
  17. Takimoto, T.; Morishita, K.; Furukawa, M.; Umeda, R.; Hatano, M. Establishment of Epstein-Barr virus (EBV) infection in epithelial cells derived from the nasopharynx by cell fusion. J. Laryngol. Otol. 1983, 97, 719–726. [Google Scholar] [CrossRef] [PubMed]
  18. Takimoto, T.; Ogura, H.; Ohno, S.; Umeda, R.; Hatano, M. Tumorigenicity of nasopharyngeal carcinoma hybrid cell line. J. Natl. Cancer Inst. 1984, 73, 711–715. [Google Scholar] [PubMed]
  19. Yip, Y.L.; Lin, W.; Deng, W.; Jia, L.; Lo, K.W.; Busson, P.; Vérillaud, B.; Liu, X.; Tsang, C.M.; Lung, M.L.; et al. Establishment of a nasopharyngeal carcinoma cell line capable of undergoing lytic Epstein-Barr virus reactivation. Lab. Investig. 2018, 98, 1093–1104. [Google Scholar] [CrossRef] [PubMed]
  20. Hui, A.B.; Cheung, S.T.; Fong, Y.; Lo, K.W.; Huang, D.P. Characterization of a new EBV-associated nasopharyngeal carcinoma cell line. Cancer Genet. Cytogenet. 1998, 101, 83–88. [Google Scholar] [CrossRef] [PubMed]
  21. Cheung, S.T.; Huang, D.P.; Hui, A.B.; Lo, K.W.; Ko, C.W.; Tsang, Y.S.; Wong, N.; Whitney, B.M.; Lee, J.C. Nasopharyngeal carcinoma cell line (C666-1) consistently harbouring Epstein-Barr virus. Int. J. Cancer 1999, 83, 121–126. [Google Scholar] [CrossRef]
  22. Chang, Y.S.; Lin, S.Y.; Lee, P.F.; Durff, T.; Chung, H.C.; Tsai, M.S. Establishment and characterization of a tumor cell line from human nasopharyngeal carcinoma tissue. Cancer Res. 1989, 49, 6752–6757. [Google Scholar] [PubMed]
  23. Establishment of an epitheloid cell line and a fusiform cell line from a patient with nasopharyngeal carcinoma. Sci. Sin. 1978, 21, 127–134.
  24. Sizhong, Z.; Xiukung, G.; Yi, Z. Cytogenetic studies on an epithelial cell line derived from poorly differentiated nasopharyngeal carcinoma. Int. J. Cancer 1983, 31, 587–590. [Google Scholar] [CrossRef] [PubMed]
  25. Kong, F.Y.; Gao, J. The invasive behavior of two human nasopharyngeal carcinoma (NPC) cell lines CNE-1, CNE-2Z in vitro. Zhonghua Bing. Li Xue Za Zhi 1991, 20, 288–291. (In Chinese) [Google Scholar]
  26. Chen, W.; Lee, Y.; Wang, H.; Yu, G.G.; Jiao, W.; Zhou, W.; Zeng, Y. Suppression of human nasopharyngeal carcinoma cell growth in nude mice by the wild-type p53 gene. J. Cancer Res. Clin. Oncol. 1992, 119, 46–48. [Google Scholar] [CrossRef] [PubMed]
  27. Prattapong, P.; Ngernsombat, C.; Aimjongjun, S.; Janvilisri, T. CRISPR/Cas9-mediated double knockout of SRPK1 and SRPK2 in a nasopharyngeal carcinoma cell line. Cancer Rep. 2020, 3, e1224. [Google Scholar] [CrossRef] [PubMed]
  28. Feng, X.P.; Yi, H.; Li, M.Y.; Li, X.H.; Yi, B.; Zhang, P.F.; Li, C.; Peng, F.; Tang, C.E.; Li, J.L.; et al. Identification of biomarkers for predicting nasopharyngeal carcinoma response to radiotherapy by proteomics. Cancer Res. 2010, 70, 3450–3462. [Google Scholar] [CrossRef] [PubMed]
  29. Klein, E.; Klein, G.; Nadkarni, J.S.; Nadkarni, J.J.; Wigzell, H.; Clifford, P. Surface IgM-kappa specificity on a Burkitt lymphoma cell in vivo and in derived culture lines. Cancer Res. 1968, 28, 1300–1310. [Google Scholar]
  30. Glaser, R.; Zhang, H.Y.; Yao, K.T.; Zhu, H.C.; Wang, F.X.; Li, G.Y.; Wen, D.S.; Li, Y.P. Two epithelial tumor cell lines (HNE-1 and HONE-1) latently infected with Epstein-Barr virus that were derived from nasopharyngeal carcinomas. Proc. Natl. Acad. Sci. USA 1989, 86, 9524–9528. [Google Scholar] [CrossRef]
  31. Chan, S.Y.; Choy, K.W.; Tsao, S.W.; Tao, Q.; Tang, T.; Chung, G.T.; Lo, K.W. Authentication of nasopharyngeal carcinoma tumor lines. Int. J. Cancer 2008, 122, 2169–2171. [Google Scholar] [CrossRef]
  32. Chang, J.Y.; Liu, J.F.; Juang, S.H.; Liu, T.W.; Chen, L.T. Novel mutation of topoisomerase I in rendering cells resistant to camptothecin. Cancer Res. 2002, 62, 3716–3721. [Google Scholar]
  33. De-Thé, G.; Ho, H.C.; Kwan, H.C.; Desgranges, C.; Favre, M.C. Nasopharyngeal carcinoma (NPC). I. Types of cultures derived from tumour biopsies and non-tumorous tissues of Chinese patients with special reference to lymphoblastoid transformation. Int. J. Cancer 1970, 6, 189–206. [Google Scholar] [CrossRef]
  34. Yata, J.; Klein, G. Some factors affecting membrane immunofluorescence reactivity of Burkitt lymphoma tissue culture cell lines. Int. J. Cancer. 1969, 4, 767–775. [Google Scholar] [CrossRef]
  35. Tsang, C.M.; Yip, Y.L.; Lo, K.W.; Deng, W.; To, K.F.; Hau, P.M.; Lau, V.M.; Takada, K.; Lui, V.W.; Lung, M.L.; et al. Cyclin D1 overexpression supports stable EBV infection in nasopharyngeal epithelial cells. Proc. Natl. Acad. Sci. USA 2012, 109, E3473–E3482. [Google Scholar] [CrossRef]
  36. Tsao, S.W.; Wang, X.; Liu, Y.; Cheung, Y.C.; Feng, H.; Zheng, Z.; Wong, N.; Yuen, P.W.; Lo, A.K.; Wong, Y.C.; et al. Establishment of two immortalized nasopharyngeal epithelial cell lines using SV40 large T and HPV16E6/E7 viral oncogenes. Biochim. Biophys. Acta 2002, 1590, 150–158. [Google Scholar] [CrossRef] [PubMed]
  37. Li, H.M.; Man, C.; Jin, Y.; Deng, W.; Yip, Y.L.; Feng, H.C.; Cheung, Y.C.; Lo, K.W.; Meltzer, P.S.; Wu, Z.G.; et al. Molecular and cytogenetic changes involved in the immortalization of nasopharyngeal epithelial cells by telomerase. Int. J. Cancer 2006, 119, 1567–1576. [Google Scholar] [CrossRef] [PubMed]
  38. Sugano, H.; Takada, M.; Chen, H.-C.; Tu, S.-M. Presence of herpes-type virus in the culture cell line from a nasopharyngeal carcinoma in Taiwan. Proc. Jpn. Acad. B Phys. Biol. Sci. 1970, 46, 453–457. [Google Scholar] [CrossRef]
  39. Chai, A.W.Y.; Yee, S.M.; Lee, H.M.; Abdul Aziz, N.; Yee, P.S.; Marzuki, M.; Wong, K.W.; Chiang, A.K.S.; Chow, L.K.; Dai, W.; et al. Establishment and characterization of an Epstein-Barr virus-positive cell line from a non-keratinizing differentiated primary nasopharyngeal carcinoma. Cancer Res. Commun. 2024, 4, 645–659. [Google Scholar] [CrossRef] [PubMed]
  40. Li, H.P.; Huang, C.Y.; Lui, K.W.; Chao, Y.K.; Yeh, C.N.; Lee, L.Y.; Huang, Y.; Lin, T.L.; Kuo, Y.C.; Huang, M.Y.; et al. Combination of epithelial growth factor receptor blockers and CDK4/6 inhibitor for nasopharyngeal carcinoma treatment. Cancers 2021, 13, 2954. [Google Scholar] [CrossRef] [PubMed]
  41. Lin, J.C.; Liao, S.K.; Lee, E.H.; Hung, M.S.; Sayion, Y.; Chen, H.C.; Kang, C.C.; Huang, L.S.; Cherng, J.M. Molecular events associated with epithelial to mesenchymal transition of nasopharyngeal carcinoma cells in the absence of Epstein-Barr virus genome. J. Biomed. Sci. 2009, 16, 105. [Google Scholar] [CrossRef] [PubMed]
  42. Liao, S.K.; Perng, Y.P.; Shen, Y.C.; Chung, P.J.; Chang, Y.S.; Wang, C.H. Chromosomal abnormalities of a new nasopharyngeal carcinoma cell line (NPC-BM1) derived from a bone marrow metastatic lesion. Cancer Genet. Cytogenet. 1998, 103, 52–58, Erratum in Cancer Genet. Cytogenet. 1998, 106, 183. [Google Scholar] [CrossRef] [PubMed]
  43. Lin, C.T.; Wong, C.I.; Chan, W.Y.; Tzung, K.W.; Ho, J.K.; Hsu, M.M.; Chuang, S.M. Establishment and characterization of two nasopharyngeal carcinoma cell lines. Lab. Investig. 1990, 62, 713–724. [Google Scholar] [PubMed]
  44. Lin, C.T.; Chan, W.Y.; Chen, W.; Huang, H.M.; Wu, H.C.; Hsu, M.M.; Chuang, S.M.; Wang, C.C. Characterization of seven newly established nasopharyngeal carcinoma cell lines. Lab. Investig. 1993, 68, 716–727. [Google Scholar] [PubMed]
  45. Teramoto, N.; Maeda, A.; Kobayashi, K.; Hayashi, K.; Oka, T.; Takahashi, K.; Takada, K.; Klein, G.; Akagi, T. Epstein-Barr virus infection to Epstein-Barr virus-negative nasopharyngeal carcinoma cell line TW03 enhances its tumorigenicity. Lab. Investig. 2000, 80, 303–312. [Google Scholar] [CrossRef] [PubMed]
  46. Yanoma, S.; Tsukuda, M.; Sawaki, S. Establishment and characterization of nasopharyngeal carcinoma cell line. Jibi Rinsho 1988, 34 (Suppl. S1), 329–333. [Google Scholar] [CrossRef]
  47. Huang, D.P.; Ho, J.H.; Poon, Y.F.; Chew, E.C.; Saw, D.; Lui, M.; Li, C.L.; Mak, L.S.; Lai, S.H.; Lau, W.H. Establishment of a cell line (NPC/HK1) from a differentiated squamous carcinoma of the nasopharynx. Int. J. Cancer 1980, 26, 127–132. [Google Scholar] [CrossRef]
  48. Lin, W.; Yip, Y.L.; Jia, L.; Deng, W.; Zheng, H.; Dai, W.; Ko, J.M.Y.; Lo, K.W.; Chung, G.T.Y.; Yip, K.Y.; et al. Establishment and characterization of new tumor xenografts and cancer cell lines from EBV-positive nasopharyngeal carcinoma. Nat. Commun. 2018, 9, 4663. [Google Scholar] [CrossRef]
  49. De Thé, G.; de Schryver, A.; Klein, G. Surface antigens on lymphoblastoid cells derived from nasopharyngeal carcinoma. Clin. Exp. Immunol. 1970, 7, 161–171. [Google Scholar]
  50. Klein, G.; Giovanella, B.; Westman, A.; Stehlin, J.S.; Mumford, D. An EBV-genome-negative cell line established from an American Burkitt lymphoma; receptor characteristics. EBV infectibility and permanent conversion into EBV-positive sublines by in vitro infection. Intervirology 1975, 5, 319–334. [Google Scholar] [CrossRef]
  51. Takimoto, T.; Sato, H.; Ogura, H.; Miyazaki, T. Establishment of an Epstein-Barr virus (EBV) genome-positive subline of Ramos (Ramos/NPC) following infection of Ramos with nasopharyngeal carcinoma (NPC)-derived EBV. Auris Nasus Larynx 1987, 14, 87–92. [Google Scholar] [CrossRef]
  52. Qian, C.N.; Berghuis, B.; Tsarfaty, G.; Bruch, M.; Kort, E.J.; Ditlev, J.; Tsarfaty, I.; Hudson, E.; Jackson, D.G.; Petillo, D.; et al. Preparing the “soil”: The primary tumor induces vasculature reorganization in the sentinel lymph node before the arrival of metastatic cancer cells. Cancer Res. 2006, 66, 10365–10376. [Google Scholar] [CrossRef]
  53. Li, C.Z.; Qian, C.N.; Chen, J.D.; Zhou, H.J.; Hao, D.L. A Visualized Nasopharyngeal Carcinoma Cell and Its Application. CN109536452A, 29 March 2019. [Google Scholar]
  54. Ye, F.; Chen, C.; Qin, J.; Liu, J.; Zheng, C. Genetic profiling reveals an alarming rate of cross-contamination among human cell lines used in China. FASEB J. 2015, 29, 4268–4272. [Google Scholar] [CrossRef] [PubMed]
  55. Dong, J.Q.; Li, M.Z.; Liu, Z.G.; Zhong, Q.; Xiong, D.; Xu, L.H.; Du, Y.; Xia, Y.F.; Zeng, M.S. Establishment and characterization of a novel nasopharyngeal carcinoma cell line (SUNE2) from a Cantonese patient. Chin. J. Cancer 2012, 31, 36–44. [Google Scholar] [CrossRef] [PubMed]
  56. Li, Q.X.; Young, L.S.; Niedobitek, G.; Dawson, C.W.; Birkenbach, M.; Wang, F.; Rickinson, A.B. Epstein-Barr virus infection and replication in a human epithelial cell system. Nature 1992, 356, 347–350. [Google Scholar] [CrossRef] [PubMed]
  57. American Type Culture Collection Standards Development Organization Workgroup ASN-0002. Cell line misidentification: The beginning of the end. Nat. Rev. Cancer 2010, 10, 441–448. [Google Scholar] [CrossRef] [PubMed]
  58. Prasad, C.P.; Tripathi, S.C.; Kumar, M.; Mohapatra, P. Passage number of cancer cell lines: Importance, intricacies, and way-forward. Biotechnol. Bioeng. 2023, 120, 2049–2055. [Google Scholar] [CrossRef] [PubMed]
  59. Hughes, P.; Marshall, D.; Reid, Y.; Parkes, H.; Gelber, C. The costs of using unauthenticated, over-passaged cell lines: How much more data do we need? Biotechniques 2007, 43, 575–586, Erratum in Biotechniques 2008, 44, 47. [Google Scholar] [CrossRef]
  60. Beckman, G.; Beckman, L.; Pontén, J.; Westermark, B. G-6-PD and PGM phenotypes of 16 continuous human tumor cell lines. Evidence against cross-contamination and contamination by HeLa cells. Hum. Hered. 1971, 21, 238–241. [Google Scholar] [CrossRef]
  61. Nelson-Rees, W.A.; Daniels, D.W.; Flandermeyer, R.R. Cross-contamination of cells in culture. Science 1981, 212, 446–452. [Google Scholar] [CrossRef]
  62. Kniss, D.A.; Summerfield, T.L. Discovery of HeLa cell contamination in HES cells: Call for cell line authentication in reproductive biology research. Reprod. Sci. 2014, 21, 1015–1019. [Google Scholar] [CrossRef]
  63. Buehring, G.C.; Eby, E.A.; Eby, M.J. Cell line cross-contamination: How aware are Mammalian cell culturists of the problem and how to monitor it? Vitr. Cell. Dev. Biol. Anim. 2004, 40, 211–215. [Google Scholar] [CrossRef]
  64. Butler, J.M. The future of forensic DNA analysis. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2015, 370, 20140252. [Google Scholar] [CrossRef]
  65. Almeida, J.L.; Korch, C.T. Authentication of human and mouse cell lines by short tandem repeat (STR) DNA genotype analysis. In Assay Guidance Manual [Internet]; Markossian, S., Grossman, A., Brimacombe, K., Arkin, M., Auld, D., Austin, C., Baell, J., Chung, T.D.Y., Coussens, N.P., Dahlin, J.L., et al., Eds.; Eli Lilly & Company and the National Center for Advancing Translational Sciences: Bethesda, MD, USA, 2004. Available online: https://www.ncbi.nlm.nih.gov/books/NBK144066/ (accessed on 16 March 2024).
  66. ASN-0002; Authentication of Human Cell Lines: Standardization of STR Profiling. ATCC Standards Development Organization: Manassas, VA, USA, 2012. Available online: https://webstore.ansi.org/preview-pages/ATCC/preview_ANSI+ATCC+ASN-0002-2011.pdf (accessed on 16 March 2024).
  67. Cabrera, C.M.; Cobo, F.; Nieto, A.; Cortés, J.L.; Montes, R.M.; Catalina, P.; Concha, A. Identity tests: Determination of cell line cross-contamination. Cytotechnology 2006, 51, 45–50. [Google Scholar] [CrossRef] [PubMed]
  68. Defendi, V.; Billingham, R.E.; Silvers, W.K.; Moorhead, P. Immunological and karyological criteria for identification of cell lines. J. Natl. Cancer Inst. 1960, 25, 359–385. [Google Scholar] [PubMed]
  69. Matsuo, Y.; Nishizaki, C.; Drexler, H.G. Efficient DNA fingerprinting method for the identification of cross-culture contamination of cell lines. Hum. Cell 1999, 12, 149–154. [Google Scholar] [PubMed]
  70. Song, L.B.; Yan, J.; Jian, S.W.; Zhang, L.; Li, M.Z.; Li, D.; Wang, H.M. Molecular mechanisms of tumorgenesis and metastasis in nasopharyngeal carcinoma cell sublines. Ai Zheng 2002, 21, 158–162. (In Chinese) [Google Scholar] [PubMed]
  71. Chen, Y.; Guo, H.; Wang, H. Effect of EBV latent membrane protein 1 gene isolated from human nasopharyngeal carcinoma cell line SUNE on the growth of immortalized epithelial cells. Zhonghua Zhong Liu Za Zhi 1998, 20, 330–332. (In Chinese) [Google Scholar]
  72. Vaughan, L.; Glänzel, W.; Korch, C.; Capes-Davis, A. Widespread use of misidentified cell line KB (HeLa): Incorrect attribution and its impact revealed through mining the scientific literature. Cancer Res. 2017, 77, 2784–2788. [Google Scholar] [CrossRef] [PubMed]
  73. Web of Science. Available online: https://www.webofscience.com (accessed on 16 March 2024).
  74. Cosme, B.; Falagan-Lotsch, P.; Ribeiro, M.; Napoleão, K.; Granjeiro, J.M.; Moura-Neto, R. Are your results valid? Cellular authentication a need from the past, an emergency on the present. Vitr. Cell. Dev. Biol. Anim. 2017, 53, 430–434. [Google Scholar] [CrossRef] [PubMed]
  75. Betsou, F.; Barnes, R.; Burke, T.; Coppola, D.; Desouza, Y.; Eliason, J.; Glazer, B.; Horsfall, D.; Kleeberger, C.; Lehmann, S.; et al. Human biospecimen research: Experimental protocol and quality control tools. Cancer Epidemiol. Biomarkers Prev. 2009, 18, 1017–1025. [Google Scholar] [CrossRef]
  76. ICLAC Register of Misidentified Cell Lines. Available online: https://iclac.org/ (accessed on 16 March 2024).
  77. Cellosaurus. Description of the Cellosaurus—A Knowledge Resource on Cell Lines. Available online: web.expasy.org/cellosaurus/description.html (accessed on 16 March 2024).
  78. Kassotis, C.D.; Hoffman, K.; Völker, J.; Pu, Y.; Veiga-Lopez, A.; Kim, S.M.; Schlezinger, J.J.; Bovolin, P.; Cottone, E.; Saraceni, A.; et al. Reproducibility of adipogenic responses to metabolism disrupting chemicals in the 3T3-L1 pre-adipocyte model system: An interlaboratory study. Toxicology 2021, 461, 152900. [Google Scholar] [CrossRef] [PubMed]
  79. Almeida, J.L.; Cole, K.D.; Plant, A.L. Standards for cell line authentication and beyond. PLoS Biol. 2016, 14, e1002476. [Google Scholar] [CrossRef] [PubMed]
  80. Weiskirchen, S.; Schröder, S.K.; Buhl, E.M.; Weiskirchen, R. A beginner’s guide to cell culture: Practical advice for preventing needless problems. Cells 2023, 12, 682. [Google Scholar] [CrossRef] [PubMed]
  81. Weiskirchen, R. Established liver cell lines: Are you sure to have the right ones? Livers 2022, 2, 171–177. [Google Scholar] [CrossRef]
Cells 13 00559 g001
Figure 1. Number of nasopharyngeal carcinoma (NPC) studies. Usage of NPC cell lines in studies published between 1970 and 2024. The data are based on a PubMed search conducted on 7 March 2024.
Figure 1. Number of nasopharyngeal carcinoma (NPC) studies. Usage of NPC cell lines in studies published between 1970 and 2024. The data are based on a PubMed search conducted on 7 March 2024.
Cells 13 00559 g001
Cells 13 00559 g002
Figure 2. Nasopharyngeal carcinoma cells (NPCs) contaminated with HeLa cell line. Usage of NPC cell lines contaminated with HeLa cells were found in studies published from 2000 to 2023. The data are derived from a PubMed search conducted on 22 January 2024.
Figure 2. Nasopharyngeal carcinoma cells (NPCs) contaminated with HeLa cell line. Usage of NPC cell lines contaminated with HeLa cells were found in studies published from 2000 to 2023. The data are derived from a PubMed search conducted on 22 January 2024.
Cells 13 00559 g002
Cells 13 00559 g003
Figure 3. Number cited and publications over time. This figure illustrates the distribution of articles that incorrectly described nasopharyngeal carcinoma cells (represented by grey bars) and the distribution of citations of these articles (represented by the black line) from 2000 to 2023. The data were obtained from Web of Science [73].
Figure 3. Number cited and publications over time. This figure illustrates the distribution of articles that incorrectly described nasopharyngeal carcinoma cells (represented by grey bars) and the distribution of citations of these articles (represented by the black line) from 2000 to 2023. The data were obtained from Web of Science [73].
Cells 13 00559 g003
Cells 13 00559 g004
Figure 4. This analysis covers scientific fields featured in articles that utilize the CNE2 cell line, as well as the distribution of these fields in articles published between 2000 and 2023. The data were derived from the Web of Science [73]. Only papers with the term “CNE2” and not “CNE-2” were considered in this analysis.
Figure 4. This analysis covers scientific fields featured in articles that utilize the CNE2 cell line, as well as the distribution of these fields in articles published between 2000 and 2023. The data were derived from the Web of Science [73]. Only papers with the term “CNE2” and not “CNE-2” were considered in this analysis.
Cells 13 00559 g004
Table 1. Number of in vitro nasopharyngeal carcinoma (NPC) studies categorized by year.
Table 1. Number of in vitro nasopharyngeal carcinoma (NPC) studies categorized by year.
YearUniform Resource Locator (URL) for Analyzed Year
1970https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%281970%29
1971https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%281971%29
1972https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%281972%29
1973https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%281973%29
1974https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%281974%29
1975https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%281975%29
1976https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%281976%29
1977https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%281977%29
1978https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%281978%29
1979https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%281979%29
1980https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%281980%29
1981https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%281981%29
1982https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%281982%29
1983https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%281983%29
1984https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%281984%29
1985https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%281985%29
1986https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%281986%29
1987https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%281987%29
1988https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%281988%29
1989https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%281989%29
1990https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%281990%29
1991https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%281991%29
1992https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%281992%29
1993https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%281993%29
1994https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%281994%29
1995https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%281995%29
1996https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%281996%29
1997https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%281997%29
1998https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%281998%29
1999https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%281999%29
2000https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%282000%29
2001https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%282001%29
2002https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%282002%29
2003https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%282003%29
2004https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%282004%29
2005https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%282005%29
2006https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%282006%29
2007https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%282007%29
2008https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%282008%29
2009https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%282009%29
2010https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%282010%29
2011https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%282011%29
2012https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%282012%29
2013https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%282013%29
2014https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%282014%29
2015https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%282015%29
2016https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%282016%29
2017https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%282017%29
2018https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%282018%29
2019https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%282019%29
2020https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%282020%29
2021https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%282021%29
2022https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%282022%29
2023https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%282023%29
2024https://pubmed.ncbi.nlm.nih.gov/?term=%28%28nasopharingeal+carcinoma%29+AND+%28cell+line%29%29+AND+%282024%29
All links were accessed on 7 March 2024.
Table 2. Immortalized human nasopharyngeal carcinoma cell lines listed in the Cellosaurus database [13].
Table 2. Immortalized human nasopharyngeal carcinoma cell lines listed in the Cellosaurus database [13].
No.Cell LineCellosaurus IDEBV StatusReference
113-9BCVCL_C527IN, LN[14]
22-27-AdCVCL_IY39IP, LN[15]
35-8FCVCL_C528IN, LN[14]
45-8F/ErbituxCVCL_S665IN, LN[16]
56-10BCVCL_C529IN, LN[14]
6A2LCVCL_X201IP[17]
7A2L/AHCVCL_X202IP[18]
8Ad-AHCVCL_X200IU, LN[18]
9C17CVCL_VT47IP[19]
10C666CVCL_M597IP, LU[20]
11C666-1CVCL_7949IP, LP[21]
12CG1CVCL_J445IP[22]
13CNE-1CVCL_6888IN, LN[23]
14CNE-2CVCL_6889IP, LN[24]
15CNE-2ZCVCL_6890IN[25]
16CNE-3CVCL_M598IN[26]
17CNE1 SRPK1 KOCVCL_YT53IN[27]
18CNE1 SRPK1/2 KOCVCL_YT55IN[27]
19CNE1 SRPK2 KOCVCL_YT54IN[27]
20CNE2-IRCVCL_C9B8IN[28]
21EstherCVCL_X932UNK[29]
22HNE-1CVCL_0308IP, LN[30]
23HNE-2CVCL_FA07LN[31]
24HNE-3CVCL_FA08LN[30]
25HONE-1CVCL_8706IP, LN[30]
26HONE-1/CPT30CVCL_M595IN[32]
27HONE-1/CPT30RCVCL_M596IN[32]
28Ly1CVCL_ZU83UNK[33]
29Ly11CVCL_ZU81UNK[33]
30Ly2CVCL_ZU84UNK[33]
31Ly28CVCL_ZU82UNK[33]
32MakuCVCL_1Q44LP[34]
33NA-NP15CVCL_DG71IN, LPNN 1
34NA-NR1CVCL_DG72IN, LPNN 1
35NA-NR15CVCL_DG73IN, LPNN 2
36NP361-CDK4R24C-hTertCVCL_B3Q4IU, LP[35]
37NP361-cyclinD1-hTertCVCL_B3Q5IU, LP[35]
38NP361hTertCVCL_B3Q3IU, LN[35]
39NP39E6/E7CVCL_F754IP, LP[36]
40NP446-CDK4R24C-hTertCVCL_B3Q6IU, LP[35]
41NP446-cyclinD1-hTertCVCL_B3Q7IU, LP[35]
42NP460hTertCVCL_X205IU, LP[37]
43NP550-CDK4R24C-hTertCVCL_B3Q8IU, LP[35]
44NP550-cyclinD1-hTertCVCL_B3Q9IU, LP[35]
45NP550hTertCVCL_B3QAIU, LN[35]
46NP69SV40TCVCL_F755IP, LP[36]
47NPC-204CVCL_A5WVIU, LN[38]
48NPC268NA 3IP, LP[39]
49NPC-B13CVCL_D3FGIU, LP[40]
50NPC-BM00CVCL_B3QCIU, LN[41]
51NPC-BM1CVCL_6007UNK[42]
52NPC-BM29CVCL_B3QBIU, LN[43]
54NPC-KTCVCL_X204IU, LP[18]
55NPC-TW01CVCL_6008IP, LN[43]
56NPC-TW02CVCL_6009IU, LN[43]
57NPC-TW03CVCL_6010IP, LN[44]
58NPC-TW03 EBV(+)CVCL_ZF72IN, LP[45]
59NPC-TW04CVCL_6011IN, LN[44]
60NPC-TW05CVCL_6012IP, LN[44]
61NPC-TW06CVCL_6013IP, LN[44]
62NPC-TW07CVCL_6014IP, LN[44]
63NPC-TW08CVCL_6015IN, LN[44]
64NPC-TW09CVCL_6016IN, LN[44]
65NPC-TY861CVCL_A5WWIP, LP[46]
66NPC/HK1CVCL_7084IN, LN[47]
67NPC38CVCL_UH63IN, LN[48]
68NPC43CVCL_UH64IP, LP[48]
69NPC53CVCL_UH65IN, LN[48]
70PatrickCVCL_IU34IP, LP[49]
71RamosCVCL_0597IN, LN[50]
72Ramos-AWCVCL_2702IN, LN[50]
73Ramos/B95-8CVCL_ZU79IN, LN[51]
74Ramos/NPCCVCL_ZU80IN, LP[51]
75S18CVCL_B0U9IN, LN[52]
76S18-1C3CVCL_B0UAIN, LN[53]
77S26CVCL_B0UBIN, LN[52]
78SilfereCVCL_W936UNK[29]
79SUNE1CVCL_6946LN[54]
80SUNE2CVCL_6956IN, LN[55]
81SVK-CR2CVCL_YD67IU, LN[56]
82SVK-NeoCVCL_YD68IU, LN[56]
1 Parent cell line: NPC-TW01. 2 Parent cell line: NA-NR1. 3 This cell line was recently established and is not yet listed in the Cellosaurus database. Abbreviations: IN, initially EBV-negative; IP, initially EBV-positive; LN, long-term culture EBV-negative; LP, long-term culture EBV-positive; LU, long-term culture EBV-status unknown; UNK, EBV status unknown.
Table 4. Table of misidentified NPC cell lines. The list is prepared according to the International Cell Line Authentication Committee (ICLAC).
Table 4. Table of misidentified NPC cell lines. The list is prepared according to the International Cell Line Authentication Committee (ICLAC).
Misidentified Cell LineICLAC-IDHistologyContaminating Cell LineActual Species
5-8F (SUNE1 derivate)ICLAC-00596poorly differentiated NPC; the highest tumorigenic and metastatic ability [70]HeLaHuman
6-10B (SUNE1 derivate)ICLAC-00597poorly differentiated NPC; the lowest tumorigenicity and lack of metastatic ability [13]HeLaHuman
CNE-1 1ICLAC-00473well-differentiated squamous cell carcinoma [22]HeLaHuman
CNE-2 1ICLAC-00474poorly differentiated NPC [24]HeLaHuman
HNE-1 2not listedpoorly differentiated squamous cell carcinoma [30]HeLaHuman
HONE-1ICLAC-00496poorly differentiated squamous cell carcinoma [30]HeLaHuman
SUNE1ICLAC-00595poorly differentiated NPC [71]HeLaHuman
SUNE2ICLAC-00598undifferentiated NPC [55]HeLaHuman
1 Also known as CNE1 and CNE2. 2 According to the Cellosaurus database, the cell line HNE-1 (CVCL-0308) has a highly similar STR profile to the cell line HONE-1 (CVCL_8706). As both cell lines were established in the same laboratory, they must be classified as misidentified.
Table 5. Citation report for misidentified nasopharyngeal carcinoma cells 1.
Table 5. Citation report for misidentified nasopharyngeal carcinoma cells 1.
NPC
Cell Line		Σ Publications
2000–2023		Year of HeLa Contamination ReportΣ Citing Article
2000–2023		Σ Citing Article (without Self-Citation)
2000–2023		Σ Times Cited 2000–2023 ReportΣ Times Cited (without Self-Citation)
2000–2023
5-8F15320151746171718951850
6-10B702015723708769748
CNE-1 225220082995292633073209
CNE-2 236120085271513959585745
HNE-16320081020100310661042
HONE112320152675264429372888
SUNE1502015472468491486
SUNE25201534343535
1 Data were taken from the Web of Science [73]. 2 Also known as CNE1 and CNE2. Summaries of the individual reports can be found at: 5-8F: https://www.webofscience.com/wos/woscc/citation-report/078cd1af-ae5b-403d-83c6-5a11501bb8d0-cad68a52 (accessed on: 22 January 2024); 6-10B: https://www.webofscience.com/wos/woscc/citation-report/8d9af056-74f5-4623-870d-a8e12e41edac-cad68016 (accessed on: 22 January 2024); CNE1: https://www.webofscience.com/wos/woscc/citation-report/3efa39d6-4463-4d0c-a51a-0a90cbd948be-c85b0591 (accessed on: 22 January 2024); CNE2: https://www.webofscience.com/wos/woscc/citation-report/a2d59c90-d979-4a24-9d54-965450e81f48-cad6478a (accessed on: 22 January 2024); HNE1: https://www.webofscience.com/wos/woscc/citation-report/cb23d688-7f35-412e-918b-cb104d4e3d0f-cad65f4f (accessed on: 22 January 2024); HONE1: https://www.webofscience.com/wos/woscc/citation-report/26af9041-724c-4ff6-adf2-4fcaa1325f98-cc481ae5 (accessed on: 22 January 2024); SUNE1: https://www.webofscience.com/wos/woscc/citation-report/fbf0dc10-a617-46bc-92b3-53420f5af93d-cad66c02 (accessed on: 22 January 2024); SUNE2: https://www.webofscience.com/wos/woscc/citation-report/9028d111-39db-445c-8950-b18b8833818e-cad67612 (accessed on: 22 January 2024).
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Makowska, A.; Weiskirchen, R. Nasopharyngeal Carcinoma Cell Lines: Reliable Alternatives to Primary Nasopharyngeal Cells? Cells 2024, 13, 559. https://doi.org/10.3390/cells13070559

AMA Style

Makowska A, Weiskirchen R. Nasopharyngeal Carcinoma Cell Lines: Reliable Alternatives to Primary Nasopharyngeal Cells? Cells. 2024; 13(7):559. https://doi.org/10.3390/cells13070559

Chicago/Turabian Style

Makowska, Anna, and Ralf Weiskirchen. 2024. "Nasopharyngeal Carcinoma Cell Lines: Reliable Alternatives to Primary Nasopharyngeal Cells?" Cells 13, no. 7: 559. https://doi.org/10.3390/cells13070559

APA Style

Makowska, A., & Weiskirchen, R. (2024). Nasopharyngeal Carcinoma Cell Lines: Reliable Alternatives to Primary Nasopharyngeal Cells? Cells, 13(7), 559. https://doi.org/10.3390/cells13070559

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop