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19 pages, 6362 KiB

Open AccessArticle

Estradiol and Estrone Have Different Biological Functions to Induce NF-κB-Driven Inflammation, EMT and Stemness in ER+ Cancer Cells

by Ana Belén Diaz-Ruano, Nuria Martinez-Alarcon, Macarena Perán, Karim Benabdellah, María de los Ángeles Garcia-Martinez, Ovidiu Preda, César Ramirez-Tortosa, Andrea Gonzalez-Hernandez, Juan Antonio Marchal and Manuel Picon-Ruiz

Int. J. Mol. Sci. 2023, 24(2), 1221; https://doi.org/10.3390/ijms24021221 - 7 Jan 2023

Cited by 8 | Viewed by 3662

Abstract

In general, the risk of being diagnosed with cancer increases with age; however, the development of estrogen-receptor-positive (ER+) cancer types in women are more closely related to menopausal status than age. In fact, the general risk factors for cancer development, such as obesity-induced [...] Read more.

In general, the risk of being diagnosed with cancer increases with age; however, the development of estrogen-receptor-positive (ER+) cancer types in women are more closely related to menopausal status than age. In fact, the general risk factors for cancer development, such as obesity-induced inflammation, show differences in their association with ER+ cancer risk in pre- and postmenopausal women. Here, we tested the role of the principal estrogens in the bloodstream before and after menopause, estradiol (E2) and estrone (E1), respectively, on inflammation, epithelial-to-mesenchymal transition (EMT) and cancer stem cell enrichment in the human ER+ cervical cancer cell line HeLa. Our results demonstrate that E1, contrary to E2, is pro-inflammatory, increases embryonic stem-transcription factors (ES-TFs) expression and induces EMT in ER+ HeLa cells. Moreover, we observed that high intratumoural expression levels of 17β-Hydroxysteroid dehydrogenase (HSD17B) isoforms involved in E1 synthesis is a poor prognosis factor, while overexpression of E2-synthetizing HSD17B isoforms is associated with a better outcome, for patients diagnosed with ER+ ovarian and uterine corpus carcinomas. This work demonstrates that E1 and E2 have different biological functions in ER+ gynaecologic cancers. These results open a new line of research in the study of ER+ cancer subtypes, highlighting the potential key oncogenic role of E1 and HSD17B E1-synthesizing enzymes in the development and progression of these diseases. Full article

(This article belongs to the Special Issue Molecular Signatures of Gynecological Cancers - Breast Cancer, Ovarian Cancer and Endometrial Cancer)

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20 pages, 8325 KiB

Open AccessArticle

Akt-Activated Endothelium Increases Cancer Cell Proliferation and Resistance to Treatment in Ovarian Cancer Cell Organoids

by Jessica Hoarau-Véchot, Morgane Blot-Dupin, Léa Pauly, Cyril Touboul, Shahin Rafii, Arash Rafii and Jennifer Pasquier

Int. J. Mol. Sci. 2022, 23(22), 14173; https://doi.org/10.3390/ijms232214173 - 16 Nov 2022

Cited by 7 | Viewed by 2479

Abstract

Ovarian cancer (OC) is a heterogeneous disease characterized by its late diagnosis (FIGO stages III and IV) and the importance of abdominal metastases often observed at diagnosis. Detached ovarian cancer cells (OCCs) float in ascites and form multicellular spheroids. Here, we developed endothelial [...] Read more.

Ovarian cancer (OC) is a heterogeneous disease characterized by its late diagnosis (FIGO stages III and IV) and the importance of abdominal metastases often observed at diagnosis. Detached ovarian cancer cells (OCCs) float in ascites and form multicellular spheroids. Here, we developed endothelial cell (EC)-based 3D spheroids to better represent in vivo conditions. When co-cultured in 3D conditions, ECs and OCCs formed organized tumor angiospheres with a core of ECs surrounded by proliferating OCCs. We established that Akt and Notch3/Jagged1 pathways played a role in angiosphere formation and peritoneum invasion. In patients’ ascites we found angiosphere-like structures and demonstrated in patients’ specimens that tumoral EC displayed Akt activation, which supports the importance of Akt activation in ECs in OC. Additionally, we demonstrated the importance of FGF2, Pentraxin 3 (PTX3), PD-ECGF and TIMP-1 in angiosphere organization. Finally, we confirmed the role of Notch3/Jagged1 in OCC–EC crosstalk relating to OCC proliferation and during peritoneal invasion. Our results support the use of multicellular spheroids to better model tumoral and stromal interaction. Such models could help decipher the complex pathways playing critical roles in metastasis spread and predict tumor response to chemotherapy or anti-angiogenic treatment. Full article

(This article belongs to the Special Issue Molecular Signatures of Gynecological Cancers - Breast Cancer, Ovarian Cancer and Endometrial Cancer)

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16 pages, 5155 KiB

Open AccessArticle

Characteristics of the Cytotoxicity of Taraxacum mongolicum and Taraxacum formosanum in Human Breast Cancer Cells

by Chien-Jung Lin, Jen-Tuo Chen, Lin-Jhen Yeh, Rong-Chi Yang, Shih-Ming Huang and Teng-Wei Chen

Int. J. Mol. Sci. 2022, 23(19), 11918; https://doi.org/10.3390/ijms231911918 - 7 Oct 2022

Cited by 4 | Viewed by 2194

Abstract

Breast cancer is a highly heterogeneous disease that has been clinically divided into three main subtypes: estrogen receptor (ER)- and progesterone receptor (PR)-positive, human epidermal growth factor receptor 2 (HER 2)-positive, and triple-negative breast cancer (TNBC). With its high metastatic potential and resistance [...] Read more.

Breast cancer is a highly heterogeneous disease that has been clinically divided into three main subtypes: estrogen receptor (ER)- and progesterone receptor (PR)-positive, human epidermal growth factor receptor 2 (HER 2)-positive, and triple-negative breast cancer (TNBC). With its high metastatic potential and resistance to endocrine therapy, HER 2-targeted therapy, and chemotherapy, TNBC represents an enormous clinical challenge. The genus Taraxacum is used to treat breast cancer in traditional medicine. Here, we applied aqueous extracts from two Taraxacum species, T. mongolicum and T. formosanum, to compare their potential antitumor effects against three human breast cancer cell lines: MDA-MB-231 (ER⁻, PR⁻, and HER2⁻), ZR-75-1 (ER⁺, PR^+/−, and HER2⁻), and MCF-7 (ER⁺, PR⁺, and HER2⁻). Our results show that T. mongolicum exerted cytotoxic effects against MDA-MB-231 cells, including the induction of apoptosis, the reduction of cell proliferation, the disruption of the mitochondrial membrane potential, and/or the downregulation of the oxygen consumption rate. Both T. mongolicum and T. formosanum decreased cell migration and colony formation in the three cell-lines and exerted suppressive effects on MCF-7 cell proliferation based on metabolic activity and BrdU incorporation, but an enhanced proliferation of ZR-75-1 cells based on BrdU incorporation. T. formosanum induced ribotoxic stress in MDA-MB-231and ZR-75-1 cells; T. mongolicum did not. In summary, these findings suggest that T. mongolicum showed greater cytotoxicity against all three tested breast cancer cell lines, especially the TNBC MDA-MB-231 cell line. Full article

(This article belongs to the Special Issue Molecular Signatures of Gynecological Cancers - Breast Cancer, Ovarian Cancer and Endometrial Cancer)

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14 pages, 2151 KiB

Open AccessArticle

Investigation of Transcriptome Patterns in Endometrial Cancers from Obese and Lean Women

by Konii Takenaka, Ashton Curry-Hyde, Ellen M. Olzomer, Rhonda Farrell, Frances L. Byrne and Michael Janitz

Int. J. Mol. Sci. 2022, 23(19), 11471; https://doi.org/10.3390/ijms231911471 - 29 Sep 2022

Cited by 4 | Viewed by 2296

Abstract

Endometrial cancer is the most common gynaecological malignancy in developed countries. One of the largest risk factors for endometrial cancer is obesity. The aim of this study was to determine whether there are differences in the transcriptome of endometrial cancers from obese vs. [...] Read more.

Endometrial cancer is the most common gynaecological malignancy in developed countries. One of the largest risk factors for endometrial cancer is obesity. The aim of this study was to determine whether there are differences in the transcriptome of endometrial cancers from obese vs. lean women. Here we investigate the transcriptome of endometrial cancer between obese and lean postmenopausal women using rRNA-depleted RNA-Seq data from endometrial cancer tissues and matched adjacent non-cancerous endometrial tissues. Differential expression analysis identified 12,484 genes (6370 up-regulated and 6114 down-regulated) in endometrial cancer tissues from obese women, and 6219 genes (3196 up-regulated and 3023 down-regulated) in endometrial cancer tissues from lean women (adjusted p-value < 0.1). A gene ontology enrichment analysis revealed that the top 1000 up-regulated genes (by adjusted p-value) were enriched for growth and proliferation pathways while the top 1000 down-regulated genes were enriched for cytoskeleton restructure networks in both obese and lean endometrial cancer tissues. In this study, we also show perturbations in the expression of protein coding genes (HIST1H2BL, HIST1H3F, HIST1H2BH, HIST1H1B, TTK, PTCHD1, ASPN, PRELP, and CDH13) and the lncRNA MBNL1-AS1 in endometrial cancer tissues. Overall, this study has identified gene expression changes that are similar and also unique to endometrial cancers from obese vs. lean women. Furthermore, some of these genes may serve as prognostic biomarkers or, possibly, therapeutic targets for endometrial cancer. Full article

(This article belongs to the Special Issue Molecular Signatures of Gynecological Cancers - Breast Cancer, Ovarian Cancer and Endometrial Cancer)

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21 pages, 5468 KiB

Open AccessArticle

Energy Substrate Transporters in High-Grade Ovarian Cancer: Gene Expression and Clinical Implications

by Marta Baczewska, Elżbieta Supruniuk, Klaudia Bojczuk, Paweł Guzik, Patrycja Milewska, Katarzyna Konończuk, Jakub Dobroch, Adrian Chabowski and Paweł Knapp

Int. J. Mol. Sci. 2022, 23(16), 8968; https://doi.org/10.3390/ijms23168968 - 11 Aug 2022

Cited by 12 | Viewed by 2778

Abstract

Ovarian cancer is a non-homogenous malignancy. High-grade serous carcinoma (HGSC) is the most common subtype, and its drug resistance mechanisms remain unclear. Despite the advantages of modern pharmacotherapy, high-grade ovarian cancer is associated with a poor prognosis and research into targeted therapies is [...] Read more.

Ovarian cancer is a non-homogenous malignancy. High-grade serous carcinoma (HGSC) is the most common subtype, and its drug resistance mechanisms remain unclear. Despite the advantages of modern pharmacotherapy, high-grade ovarian cancer is associated with a poor prognosis and research into targeted therapies is in progress. The aim of the study was to assess the dominant energy substrate transport mechanism in ovarian cancer cells and to verify whether genomic aberrations could predict clinical outcomes using the Cancer Genome Atlas (TCGA) dataset. Total RNA was extracted from HGSC frozen tissues, and the expression of selected genes was compared to respective controls. GLUT1, FABPpm, MCT4 and SNAT1 genes were significantly overexpressed in carcinomas compared with controls, while expression of CD36/SR-B2, FATP1, FABP4, GLUT4, ASCT2 and LPL was decreased. No differences were found in FATP4, LAT1, MCT1 and FASN. The transcript content of mitochondrial genes such as PGC-1α, TFAM and COX4/1 was similar between groups, while the β-HAD level declined in ovarian cancer. Additionally, the MCT4 level was reduced and PGC-1α was elevated in cancer tissue from patients with ‘small’ primary tumor and omental invasion accompanied by ascites as compared to patients that exhibited greater tendencies to metastasize to lymph nodes with clear omentum. Based on TCGA, higher FABP4 and LPL and lower TFAM expression indicated poorer overall survival in patients with ovarian cancer. In conclusion, the presented data show that there is no exclusive energy substrate in HGSC. However, this study indicates the advantage of glucose and lactate transport over fatty acids, thereby suggesting potential therapeutic intervention targets to impede ovarian cancer growth. Full article

(This article belongs to the Special Issue Molecular Signatures of Gynecological Cancers - Breast Cancer, Ovarian Cancer and Endometrial Cancer)

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12 pages, 1849 KiB

Open AccessArticle

Size and Methylation Index of Cell-Free and Cell-Surface-Bound DNA in Blood of Breast Cancer Patients in the Contest of Liquid Biopsy

by Svetlana Tamkovich, Alexey Tupikin, Anton Kozyakov and Pavel Laktionov

Int. J. Mol. Sci. 2022, 23(16), 8919; https://doi.org/10.3390/ijms23168919 - 10 Aug 2022

Cited by 5 | Viewed by 2090

Abstract

Aberrantly methylated circulating DNA (cirDNA) has proven to be a good cancer marker, but its detection is limited by low concentrations, fragmentation, and insufficiency. Since the methylated cirDNA was shown to be more stable in circulation than the unmethylated one and was shown [...] Read more.

Aberrantly methylated circulating DNA (cirDNA) has proven to be a good cancer marker, but its detection is limited by low concentrations, fragmentation, and insufficiency. Since the methylated cirDNA was shown to be more stable in circulation than the unmethylated one and was shown to bind with the blood cell surface, we studied the concentration, representation, and fragmentation of tumor-derived methylated DNA in cell-free and cell-surface-associated DNA. We found that long DNA fragments (more than 10 kb) are mainly associated with the surface of blood cells. However, in plasma short DNA fragments (100–1000 bp) were also found along with long DNA fragments. Isolation of short fragments after separation of cirDNA in 6% PAGE followed by quantitative PCR (L1 element) has shown that short DNA fragments in healthy females represent 22% versus 0.5–4.4% in breast cancer patients. The methylated form of the RARβ2 gene was detected only in long DNA fragments by Real-time TaqMan PCR of bisulfite-converted DNA. The methylation index of cirDNA from healthy women was estimated at 0%, 9%, and 7% in plasma, PBS-EDTA, and trypsin eluates from the surface of blood cells, respectively. The methylation index of breast cancer patients’ DNA was found to be 33%, 15%, and 61% in the same fractions confirming the overrepresentation of methylated DNA in csbDNA. Full article

(This article belongs to the Special Issue Molecular Signatures of Gynecological Cancers - Breast Cancer, Ovarian Cancer and Endometrial Cancer)

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21 pages, 2911 KiB

Open AccessArticle

ACBD3 Bioinformatic Analysis and Protein Expression in Breast Cancer Cells

by Jack Houghton-Gisby, Rachel Kerslake, Emmanouil Karteris, Kefah Mokbel and Amanda J. Harvey

Int. J. Mol. Sci. 2022, 23(16), 8881; https://doi.org/10.3390/ijms23168881 - 10 Aug 2022

Cited by 3 | Viewed by 2648

Abstract

ACBD3 overexpression has previously been found to correlate with worse prognosis for breast cancer patients and, as an incredibly diverse protein in both function and cellular localisation, ACBD3 may have a larger role in breast cancer than previously thought. This study further investigated [...] Read more.

ACBD3 overexpression has previously been found to correlate with worse prognosis for breast cancer patients and, as an incredibly diverse protein in both function and cellular localisation, ACBD3 may have a larger role in breast cancer than previously thought. This study further investigated ACBD3′s role in breast cancer. Bioinformatic databases were queried to characterise ACBD3 expression and mutation in breast cancer and to investigate how overexpression affects breast cancer patient outcomes. Immunohistochemistry was carried out to examine ACBD3 location within cells and tissue structures. ACBD3 was more highly expressed in breast cancer than in any other cancer or matched normal tissue, and expression over the median level resulted in reduced relapse-free, overall, and distant metastasis-free survival for breast cancer patients as a whole, with some differences observed between subtypes. IHC analysis found that ACBD3 levels varied based on hormone receptor status, indicating that ACBD3 could be a candidate biomarker for poor patient prognosis in breast cancer and may possibly be a biomarker for ER signal reprogramming of precancerous breast tissue. Full article

(This article belongs to the Special Issue Molecular Signatures of Gynecological Cancers - Breast Cancer, Ovarian Cancer and Endometrial Cancer)

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11 pages, 3441 KiB

Open AccessArticle

Aryl Hydrocarbon Receptor Promotes Cell Growth, Stemness Like Characteristics, and Metastasis in Human Ovarian Cancer via Activation of PI3K/Akt, β-Catenin, and Epithelial to Mesenchymal Transition Pathways

by Lubna Therachiyil, Roopesh Krishnankutty, Fareed Ahmad, Jericha M. Mateo, Shahab Uddin and Hesham M. Korashy

Int. J. Mol. Sci. 2022, 23(12), 6395; https://doi.org/10.3390/ijms23126395 - 7 Jun 2022

Cited by 18 | Viewed by 2830

Abstract

Ovarian cancer (OC) ranks first in cancer-related deaths out of all female reproductive malignancies with high-pitched tumor relapse and chemoresistance. Several reports correlate cancer occurrences with exposure to xenobiotics via induction of a protein receptor named aryl hydrocarbon receptor (AhR). However, the effect [...] Read more.

Ovarian cancer (OC) ranks first in cancer-related deaths out of all female reproductive malignancies with high-pitched tumor relapse and chemoresistance. Several reports correlate cancer occurrences with exposure to xenobiotics via induction of a protein receptor named aryl hydrocarbon receptor (AhR). However, the effect of AhR on OC proliferation, expansion, and chemoresistance remains unrevealed. For this purpose, OC cells A2780 and A2780cis cells were treated with AhR activator, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and the effects were determined by Real-Time Cell Analyzer, clonogenic assay, flow cytometry, immunoblotting and wound healing assay. Our results showed that activation of AhR by TCDD in A2780 cells induced the PI3K/AKT pathway followed by induction of anti-apoptotic proteins BCL-2, BCL-xl, and MCL-1. In addition, a significant increase in stemness marker aldehyde dehydrogenase (ALDH1) was observed. This effect was also associated with an accumulation of β-catenin, a Wnt transcription factor. Moreover, we observed induction of epithelial to mesenchymal transition (EMT) upon AhR activation. In conclusion, the results from the current study confirm that AhR mediates OC progression, stemness characteristics, and metastatic potential via activation of PI3K/Akt, Wnt/β-catenin, and EMT. This study provides a better insight into the modulatory role of AhR that might help in developing novel therapeutic strategies for OC treatment. Full article

(This article belongs to the Special Issue Molecular Signatures of Gynecological Cancers - Breast Cancer, Ovarian Cancer and Endometrial Cancer)

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22 pages, 3071 KiB

Open AccessArticle

Genomic Validation of Endometrial Cancer Patient-Derived Xenograft Models as a Preclinical Tool

by Beatriz Villafranca-Magdalena, Carina Masferrer-Ferragutcasas, Carlos Lopez-Gil, Eva Coll-de la Rubia, Marta Rebull, Genis Parra, Ángel García, Armando Reques, Silvia Cabrera, Eva Colas, Antonio Gil-Moreno and Cristian P. Moiola

Int. J. Mol. Sci. 2022, 23(11), 6266; https://doi.org/10.3390/ijms23116266 - 3 Jun 2022

Cited by 6 | Viewed by 2852

Abstract

Endometrial cancer (EC) is the second most frequent gynecological cancer worldwide. Although improvements in EC classification have enabled an accurate establishment of disease prognosis, women with a high-risk or recurrent EC face a dramatic situation due to limited further treatment options. Therefore, new [...] Read more.

Endometrial cancer (EC) is the second most frequent gynecological cancer worldwide. Although improvements in EC classification have enabled an accurate establishment of disease prognosis, women with a high-risk or recurrent EC face a dramatic situation due to limited further treatment options. Therefore, new strategies that closely mimic the disease are required to maximize drug development success. Patient-derived xenografts (PDXs) are widely recognized as a physiologically relevant preclinical model. Hence, we propose to molecularly and histologically validate EC PDX models. To reveal the molecular landscape of PDXs generated from 13 EC patients, we performed histological characterization and whole-exome sequencing analysis of tumor samples. We assessed the similarity between PDXs and their corresponding patient’s tumor and, additionally, to an extended cohort of EC patients obtained from The Cancer Genome Atlas (TCGA). Finally, we performed functional enrichment analysis to reveal differences in molecular pathway activation in PDX models. We demonstrated that the PDX models had a well-defined and differentiated molecular profile that matched the genomic profile described by the TCGA for each EC subtype. Thus, we validated EC PDX’s potential to reliably recapitulate the majority of histologic and molecular EC features. This work highlights the importance of a thorough characterization of preclinical models for the improvement of the success rate of drug-screening assays for personalized medicine. Full article

(This article belongs to the Special Issue Molecular Signatures of Gynecological Cancers - Breast Cancer, Ovarian Cancer and Endometrial Cancer)

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16 pages, 23213 KiB

Open AccessArticle

JAK2-Mediated Phosphorylation of Stress-Induced Phosphoprotein-1 (STIP1) in Human Cells

by Angel Chao, Min-Jie Liao, Shun-Hua Chen, Yun-Shien Lee, Chi-Neu Tsai, Chiao-Yun Lin and Chia-Lung Tsai

Int. J. Mol. Sci. 2022, 23(5), 2420; https://doi.org/10.3390/ijms23052420 - 22 Feb 2022

Cited by 8 | Viewed by 3059

Abstract

Stress-induced phosphoprotein-1 (STIP1)—a heat shock protein (HSP)70/HSP90 adaptor protein—is commonly overexpressed in malignant cells, where it controls proliferation via multiple signaling pathways, including JAK2/STAT3. We have previously shown that STIP1 stabilizes the protein tyrosine kinase JAK2 in cancer cells via HSP90 binding. In [...] Read more.

Stress-induced phosphoprotein-1 (STIP1)—a heat shock protein (HSP)70/HSP90 adaptor protein—is commonly overexpressed in malignant cells, where it controls proliferation via multiple signaling pathways, including JAK2/STAT3. We have previously shown that STIP1 stabilizes the protein tyrosine kinase JAK2 in cancer cells via HSP90 binding. In this study, we demonstrate that STIP1 may act as a substrate for JAK2 and that phosphorylation of tyrosine residues 134 and 152 promoted STIP1 protein stability, induced its nuclear-cytoplasmic shuttling, and promoted its secretion into the extracellular space. We also found that JAK2-mediated STIP1 phosphorylation enhanced cell viability and increased resistance to cisplatin-induced cell death. Conversely, interference STIP1 with JAK2 interaction—attained either through site-directed mutagenesis or the use of cell-penetrating peptides—decreased JAK2 protein levels, ultimately leading to cell death. On analyzing human ovarian cancer specimens, JAK2 and STIP1 expression levels were found to be positively correlated with each other. Collectively, these results indicate that JAK2-mediated phosphorylation of STIP-1 is critical for sustaining the JAK2/STAT3 signaling pathway in cancer cells. Full article

(This article belongs to the Special Issue Molecular Signatures of Gynecological Cancers - Breast Cancer, Ovarian Cancer and Endometrial Cancer)

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Review

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12 pages, 271 KiB

Open AccessReview

Human RNASET2: A Highly Pleiotropic and Evolutionary Conserved Tumor Suppressor Gene Involved in the Control of Ovarian Cancer Pathogenesis

by Antonino Bruno, Douglas M. Noonan, Roberto Valli, Giovanni Porta, Roberto Taramelli, Lorenzo Mortara and Francesco Acquati

Int. J. Mol. Sci. 2022, 23(16), 9074; https://doi.org/10.3390/ijms23169074 - 13 Aug 2022

Cited by 5 | Viewed by 2021

Abstract

Ovarian cancer represents one of the most malignant gynecological cancers worldwide, with an overall 5-year survival rate, being locked in the 25–30% range in the last decade. Cancer immunotherapy is currently one of the most intensively investigated and promising therapeutic strategy and as [...] Read more.

Ovarian cancer represents one of the most malignant gynecological cancers worldwide, with an overall 5-year survival rate, being locked in the 25–30% range in the last decade. Cancer immunotherapy is currently one of the most intensively investigated and promising therapeutic strategy and as such, is expected to provide in the incoming years significant benefits for ovarian cancer treatment as well. Here, we provide a detailed survey on the highly pleiotropic oncosuppressive roles played by the human RNASET2 gene, whose protein product has been consistently reported to establish a functional crosstalk between ovarian cancer cells and key cellular effectors of the innate immune system (the monocyte/macrophages lineage), which is in turn able to promote the recruitment to the cancer tissue of M1-polarized, antitumoral macrophages. This feature, coupled with the ability of T2 ribonucleases to negatively affect several cancer-related parameters in a cell-autonomous manner on a wide range of ovarian cancer experimental models, makes human RNASET2 a very promising candidate to develop a “multitasking” therapeutic approach for innovative future applications for ovarian cancer treatment. Full article

(This article belongs to the Special Issue Molecular Signatures of Gynecological Cancers - Breast Cancer, Ovarian Cancer and Endometrial Cancer)

19 pages, 2414 KiB

Open AccessReview

Exosomes in Breast Cancer: Involvement in Tumor Dissemination and Prospects for Liquid Biopsy

by Aleksei Shefer, Alena Yalovaya and Svetlana Tamkovich

Int. J. Mol. Sci. 2022, 23(16), 8845; https://doi.org/10.3390/ijms23168845 - 9 Aug 2022

Cited by 7 | Viewed by 3954

Abstract

In women, breast cancer (BC) is the most commonly diagnosed cancer (24.5%) and the leading cause of cancer death (15.5%). Understanding how this heterogeneous disease develops and the confirm mechanisms behind tumor progression is of utmost importance. Exosomes are long-range message vesicles that [...] Read more.

In women, breast cancer (BC) is the most commonly diagnosed cancer (24.5%) and the leading cause of cancer death (15.5%). Understanding how this heterogeneous disease develops and the confirm mechanisms behind tumor progression is of utmost importance. Exosomes are long-range message vesicles that mediate communication between cells in physiological conditions but also in pathology, such as breast cancer. In recent years, there has been an exponential rise in the scientific studies reporting the change in morphology and cargo of tumor-derived exosomes. Due to the transfer of biologically active molecules, such as RNA (microRNA, long non-coding RNA, mRNA, etc.) and proteins (transcription factors, enzymes, etc.) into recipient cells, these lipid bilayer 30–150 nm vesicles activate numerous signaling pathways that promote tumor development. In this review, we attempt to shed light on exosomes’ involvement in breast cancer pathogenesis (including epithelial-to-mesenchymal transition (EMT), tumor cell proliferation and motility, metastatic processes, angiogenesis stimulation, and immune system repression). Moreover, the potential use of exosomes as promising diagnostic biomarkers for liquid biopsy of breast cancer is also discussed. Full article

(This article belongs to the Special Issue Molecular Signatures of Gynecological Cancers - Breast Cancer, Ovarian Cancer and Endometrial Cancer)

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52 pages, 4322 KiB

Open AccessReview

Cancer Stem Cells in Ovarian Cancer—A Source of Tumor Success and a Challenging Target for Novel Therapies

by Jacek R Wilczyński, Miłosz Wilczyński and Edyta Paradowska

Int. J. Mol. Sci. 2022, 23(5), 2496; https://doi.org/10.3390/ijms23052496 - 24 Feb 2022

Cited by 31 | Viewed by 5503

Abstract

Ovarian cancer is the most lethal neoplasm of the female genital organs. Despite indisputable progress in the treatment of ovarian cancer, the problems of chemo-resistance and recurrent disease are the main obstacles for successful therapy. One of the main reasons for this is [...] Read more.

Ovarian cancer is the most lethal neoplasm of the female genital organs. Despite indisputable progress in the treatment of ovarian cancer, the problems of chemo-resistance and recurrent disease are the main obstacles for successful therapy. One of the main reasons for this is the presence of a specific cell population of cancer stem cells. The aim of this review is to show the most contemporary knowledge concerning the biology of ovarian cancer stem cells (OCSCs) and their impact on chemo-resistance and prognosis in ovarian cancer patients, as well as to present the treatment options targeted exclusively on the OCSCs. The review presents data concerning the role of cancer stem cells in general and then concentrates on OCSCs. The surface and intracellular OCSCs markers and their meaning both for cancer biology and clinical prognosis, signaling pathways specifically activated in OCSCs, the genetic and epigenetic regulation of OCSCs function including the recent studies on the non-coding RNA regulation, cooperation between OCSCs and the tumor microenvironment (ovarian cancer niche) including very specific environment such as ascites fluid, the role of shear stress, autophagy and metabolic changes for the function of OCSCs, and finally mechanisms of OCSCs escape from immune surveillance, are described and discussed extensively. The possibilities of anti-OCSCs therapy both in experimental settings and in clinical trials are presented, including the recent II phase clinical trials and immunotherapy. OCSCs are a unique population of cancer cells showing a great plasticity, self-renewal potential and resistance against anti-cancer treatment. They are responsible for the progression and recurrence of the tumor. Several completed and ongoing clinical trials have tested different anti-OCSCs drugs which, however, have shown unsatisfactory efficacy in most cases. We propose a novel approach to ovarian cancer diagnosis and therapy. Full article

(This article belongs to the Special Issue Molecular Signatures of Gynecological Cancers - Breast Cancer, Ovarian Cancer and Endometrial Cancer)

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