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Chemical Modulation and Analytical Detection of Cancer Stem Cells, Circulating...
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Chemical Modulation and Analytical Detection of Cancer Stem Cells, Circulating Tumour Cells, and Other Non-bulk Cancer Cell Types

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Survivorship and Quality of Life".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 28866

Special Issue Editor

Dr. Kogularamanan Suntharalingam

E-Mail Website
Guest Editor
School of Chemistry, University of Leicester, University Road, Leicester LE1 7RH, UK
Interests: metallopharmaceuticals; metallodrugs; biorganometallic complexes; biologically-active metal clusters; metal-based drug delivery agents; cancer metallomics; metal–protein interactions; metal–nucleic acid interactions; theranostics metal complexes; cancer imaging agents
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer stem cells (CSCs) are a distinct sub-population of tumour cells that have the ability to self-renew, differentiate, and form secondary tumours. CSCs effectively evade conventional chemotherapy and radiotherapy as these treatments specifically target fast growing cancer cells, and CSCs, due to their stem cell-like properties, divide more slowly. After surviving treatment, CSCs are able to regenerate the original tumour and/or produce invasive cancer cells that are able to colonise distant organs. Circulating tumour cells (CTCs) are the source of metastases. CTCs break away from primary tumour sites into the circulatory or lymphatic system and move around the body, ultimately settling and infecting distant organs. Heterogeneity within CTCs indicates that CTC sub-populations can display CSC-like properties. Indeed, these cell types share some cell surface markers and phenotypes. Both CSCs and CTCs are widely thought to be responsible for cancer relapse and metastasis. Given our current clinical understanding, it is evident that one must be able to detect and/or remove CSCs and CTCs at the earliest possible opportunity (during cancer progression), to prevent tumour spread and thus provide positive outcomes. This Special Issue of Cancers aims to showcase recent advancements in any aspect of the chemical modulation or analytical detection of CSCs, CTCs, and other metastasis-related non-bulk cancer cell types. Chemical, analytical, diagnostic, biophysical, in vitro, and in vivo studies are all welcome. Review articles that describe the current and upcoming strategies for isolating, detecting, or treating CSCs and CTCs, in any context, are also welcome.

Dr. Kogularamanan Suntharalingam
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Cancer stem cells
  • circulating tumour cells
  • early cancer detection
  • chemical modulation
  • cancer analytics
  • cancer diagnostics.

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Published Papers (6 papers)

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Research

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15 pages, 5482 KiB  
Article
Exosomal HMGB1 Promoted Cancer Malignancy
by Jiaan-Der Wang, Ya-Yu Wang, Shih-Yi Lin, Cheng-Yi Chang, Jian-Ri Li, Shi-Wei Huang, Wen-Ying Chen, Su-Lan Liao and Chun-Jung Chen
Cancers 2021, 13(4), 877; https://doi.org/10.3390/cancers13040877 - 19 Feb 2021
Cited by 13 | Viewed by 3940
Abstract
Reciprocal crosstalk between platelets and malignancies underscores the potential of antiplatelet therapy in cancer treatment. In this study, we found that human chronic myeloid leukemia K562 cell-differentiated megakaryocytes and murine platelets produced bioactive substances and these are released into the extracellular space, partly [...] Read more.
Reciprocal crosstalk between platelets and malignancies underscores the potential of antiplatelet therapy in cancer treatment. In this study, we found that human chronic myeloid leukemia K562 cell-differentiated megakaryocytes and murine platelets produced bioactive substances and these are released into the extracellular space, partly in their exosomal form. High-mobility group box 1 (HMGB1) is a type of exosomal cargo, and the antiplatelet drugs aspirin and dipyridamole interfered with its incorporation into the exosomes. Those released substances and exosomes, along with exogenous HMGB1, promoted cancer cell survival and protected cells from doxorubicin cytotoxicity. In a tumor-bearing model established using murine Lewis lung carcinoma (LLC) cells and C57BL/6 mice, the tumor suppressive effect of dipyridamole correlated well with decreased circulating white blood cells, soluble P-selectin, TGF-β1 (Transforming Growth Factor-β1), exosomes, and exosomal HMGB1, as well as tumor platelet infiltration. Exosome release inhibitor GW4869 exhibited suppressive effects as well. The suppressive effect of dipyridamole on cancer cell survival was paralleled by a reduction of HMGB1/receptor for advanced glycation end-products axis, and proliferation- and migration-related β-catenin, Yes-associated protein 1, Runt-related transcription factor 2, and TGF- β1/Smad signals. Therefore, exosomes and exosomal HMGB1 appear to have roles in platelet-driven cancer malignancy and represent targets of antiplatelet drugs in anticancer treatment. Full article
(This article belongs to the Special Issue Chemical Modulation and Analytical Detection of Cancer Stem Cells, Circulating Tumour Cells, and Other Non-bulk Cancer Cell Types)
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Review

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15 pages, 848 KiB  
Review
Autophagy Regulation on Cancer Stem Cell Maintenance, Metastasis, and Therapy Resistance
by Xin Wang, Jihye Lee and Changqing Xie
Cancers 2022, 14(2), 381; https://doi.org/10.3390/cancers14020381 - 13 Jan 2022
Cited by 23 | Viewed by 4122
Abstract
Cancer stem cells (CSCs) are a subset of the tumor population that play critical roles in tumorigenicity, metastasis, and relapse. A key feature of CSCs is their resistance to numerous therapeutic strategies which include chemotherapy, radiation, and immune checkpoint inhibitors. In recent years, [...] Read more.
Cancer stem cells (CSCs) are a subset of the tumor population that play critical roles in tumorigenicity, metastasis, and relapse. A key feature of CSCs is their resistance to numerous therapeutic strategies which include chemotherapy, radiation, and immune checkpoint inhibitors. In recent years, there is a growing body of literature that suggests a link between CSC maintenance and autophagy, a mechanism to recycle intracellular components during moments of environmental stress, especially since CSCs thrive in a tumor microenvironment that is plagued with hypoxia, acidosis, and lack of nutrients. Autophagy activation has been shown to aid in the upkeep of a stemness state along with bolstering resistance to cancer treatment. However, recent studies have also suggested that autophagy is a double-edged sword with anti-tumorigenic properties under certain circumstances. This review summarizes and integrates what has been published in the literature in terms of what role autophagy plays in stemness maintenance of CSCs and suggests that there is a more complex interplay between autophagy and apoptosis which involves multiple pathways of regulation. Future cancer therapy strategies are needed to eradicate this resistant subset of the cell population through autophagy regulation. Full article
(This article belongs to the Special Issue Chemical Modulation and Analytical Detection of Cancer Stem Cells, Circulating Tumour Cells, and Other Non-bulk Cancer Cell Types)
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15 pages, 853 KiB  
Review
Clinical Relevance of Mesenchymal- and Stem-Associated Phenotypes in Circulating Tumor Cells Isolated from Lung Cancer Patients
by Evangelia Pantazaka, Vasileios Vardas, Argyro Roumeliotou, Stavros Kakavogiannis and Galatea Kallergi
Cancers 2021, 13(9), 2158; https://doi.org/10.3390/cancers13092158 - 29 Apr 2021
Cited by 31 | Viewed by 3232
Abstract
Lung cancer is the leading cause of cancer-related mortality globally. Among the types of lung cancer, non-small-cell lung cancer (NSCLC) is more common, while small-cell lung cancer (SCLC) is less frequent yet more aggressive. Circulating tumor cells (CTCs), albeit rare, have been portrayed [...] Read more.
Lung cancer is the leading cause of cancer-related mortality globally. Among the types of lung cancer, non-small-cell lung cancer (NSCLC) is more common, while small-cell lung cancer (SCLC) is less frequent yet more aggressive. Circulating tumor cells (CTCs), albeit rare, have been portrayed as essential players in the progression of lung cancer. CTCs are considered to adopt an epithelial-to-mesenchymal transition (EMT) phenotype and characteristics of cancer stem cells (CSCs). This EMT (or partial) phenotype affords these cells the ability to escape from the primary tumor, travel into the bloodstream, and survive extremely adverse conditions, before colonizing distant foci. Acquisition of CSC features, such as self-renewal, differentiation, and migratory potential, further reflect CTCs’ invasive potential. CSCs have been identified in lung cancer, and expression of EMT markers has previously been correlated with poor clinical outcomes. Thus far, a vast majority of studies have concentrated on CTC detection and enumeration as a prognostic tools of patients’ survival or for monitoring treatment efficacy. In this review, we highlight EMT and CSC markers in CTCs and focus on the clinical significance of these phenotypes in the progression of both non-small- and small-cell lung cancer. Full article
(This article belongs to the Special Issue Chemical Modulation and Analytical Detection of Cancer Stem Cells, Circulating Tumour Cells, and Other Non-bulk Cancer Cell Types)
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17 pages, 4882 KiB  
Review
Microfluidic Chip-Based Cancer Diagnosis and Prediction of Relapse by Detecting Circulating Tumor Cells and Circulating Cancer Stem Cells
by Hyeon-Yeol Cho, Jin-Ha Choi, Joungpyo Lim, Sang-Nam Lee and Jeong-Woo Choi
Cancers 2021, 13(6), 1385; https://doi.org/10.3390/cancers13061385 - 18 Mar 2021
Cited by 24 | Viewed by 4785
Abstract
Detecting circulating tumor cells (CTCs) has been considered one of the best biomarkers in liquid biopsy for early diagnosis and prognosis monitoring in cancer. A major challenge of using CTCs is detecting extremely low-concentrated targets in the presence of high noise factors such [...] Read more.
Detecting circulating tumor cells (CTCs) has been considered one of the best biomarkers in liquid biopsy for early diagnosis and prognosis monitoring in cancer. A major challenge of using CTCs is detecting extremely low-concentrated targets in the presence of high noise factors such as serum and hematopoietic cells. This review provides a selective overview of the recent progress in the design of microfluidic devices with optical sensing tools and their application in the detection and analysis of CTCs and their small malignant subset, circulating cancer stem cells (CCSCs). Moreover, discussion of novel strategies to analyze the differentiation of circulating cancer stem cells will contribute to an understanding of metastatic cancer, which can help clinicians to make a better assessment. We believe that the topic discussed in this review can provide brief guideline for the development of microfluidic-based optical biosensors in cancer prognosis monitoring and clinical applications. Full article
(This article belongs to the Special Issue Chemical Modulation and Analytical Detection of Cancer Stem Cells, Circulating Tumour Cells, and Other Non-bulk Cancer Cell Types)
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31 pages, 4958 KiB  
Review
The Role of Autophagy and lncRNAs in the Maintenance of Cancer Stem Cells
by Leila Jahangiri, Tala Ishola, Perla Pucci, Ricky M. Trigg, Joao Pereira, John A. Williams, Megan L. Cavanagh, Georgios V. Gkoutos, Loukia Tsaprouni and Suzanne D. Turner
Cancers 2021, 13(6), 1239; https://doi.org/10.3390/cancers13061239 - 11 Mar 2021
Cited by 14 | Viewed by 4225
Abstract
Cancer stem cells (CSCs) possess properties such as self-renewal, resistance to apoptotic cues, quiescence, and DNA-damage repair capacity. Moreover, CSCs strongly influence the tumour microenvironment (TME) and may account for cancer progression, recurrence, and relapse. CSCs represent a distinct subpopulation in tumours and [...] Read more.
Cancer stem cells (CSCs) possess properties such as self-renewal, resistance to apoptotic cues, quiescence, and DNA-damage repair capacity. Moreover, CSCs strongly influence the tumour microenvironment (TME) and may account for cancer progression, recurrence, and relapse. CSCs represent a distinct subpopulation in tumours and the detection, characterisation, and understanding of the regulatory landscape and cellular processes that govern their maintenance may pave the way to improving prognosis, selective targeted therapy, and therapy outcomes. In this review, we have discussed the characteristics of CSCs identified in various cancer types and the role of autophagy and long noncoding RNAs (lncRNAs) in maintaining the homeostasis of CSCs. Further, we have discussed methods to detect CSCs and strategies for treatment and relapse, taking into account the requirement to inhibit CSC growth and survival within the complex backdrop of cellular processes, microenvironmental interactions, and regulatory networks associated with cancer. Finally, we critique the computationally reinforced triangle of factors inclusive of CSC properties, the process of autophagy, and lncRNA and their associated networks with respect to hypoxia, epithelial-to-mesenchymal transition (EMT), and signalling pathways. Full article
(This article belongs to the Special Issue Chemical Modulation and Analytical Detection of Cancer Stem Cells, Circulating Tumour Cells, and Other Non-bulk Cancer Cell Types)
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33 pages, 1564 KiB  
Review
A Review of Circulating Tumour Cell Enrichment Technologies
by Amelia J. Rushton, Georgios Nteliopoulos, Jacqueline A. Shaw and R. Charles Coombes
Cancers 2021, 13(5), 970; https://doi.org/10.3390/cancers13050970 - 26 Feb 2021
Cited by 115 | Viewed by 7584
Abstract
Circulating tumour cells (CTCs) are the precursor cells for the formation of metastatic disease. With a simple blood draw, liquid biopsies enable the non-invasive sampling of CTCs from the blood, which have the potential to provide important insights into cancer detection and monitoring. [...] Read more.
Circulating tumour cells (CTCs) are the precursor cells for the formation of metastatic disease. With a simple blood draw, liquid biopsies enable the non-invasive sampling of CTCs from the blood, which have the potential to provide important insights into cancer detection and monitoring. Since gaining FDA approval in 2004, the CellSearch system has been used to determine the prognosis of patients with metastatic breast, prostate and colorectal cancers. This utilises the cell surface marker Epithelial Cell Adhesion Molecule (EpCAM), to enrich CTCs, and many other technologies have adopted this approach. More recently, the role of mesenchymal-like CTCs in metastasis formation has come to light. It has been suggested that these cells are more aggressive metastatic precursors than their epithelial counterparts; however, mesenchymal CTCs remain undetected by EpCAM-based enrichment methods. This has prompted the development of a variety of ‘label free’ enrichment technologies, which exploit the unique physical properties of CTCs (such as size and deformability) compared to other blood components. Here, we review a wide range of both immunocapture and label free CTC enrichment technologies, summarising the most significant advantages and disadvantages of each. We also highlight the important characteristics that technologies should possess for routine clinical use, since future developments could have important clinical implications, with the potential to direct personalised therapies for patients with cancer. Full article
(This article belongs to the Special Issue Chemical Modulation and Analytical Detection of Cancer Stem Cells, Circulating Tumour Cells, and Other Non-bulk Cancer Cell Types)
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