Tumor-Initiating Cells in Ovarian Cancer

2018 ◽  
pp. 61-71
Author(s):  
Sharmila A. Bapat
Keyword(s):  
Ovarian Cancer ◽  
Tumor Initiating Cells

scholarly journals Characterization of SOX2, OCT4 and NANOG in Ovarian Cancer Tumor-Initiating Cells

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 262
Author(s):  
Mikella Robinson ◽  
Samuel F. Gilbert ◽  
Jennifer A. Waters ◽  
Omar Lujano-Olazaba ◽  
Jacqueline Lara ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Chemotherapy Resistance ◽  
Tumor Initiating Cells ◽  
In Vivo Experiments ◽  
Nanog Expression ◽  
Ovarian Cancer Cell Lines ◽  
Cancer Tumor ◽  
Early Tumor ◽  
Cycle Regulation

The identification of tumor-initiating cells (TICs) has traditionally relied on surface markers including CD133, CD44, CD117, and the aldehyde dehydrogenase (ALDH) enzyme, which have diverse expression across samples. A more reliable indication of TICs may include the expression of embryonic transcription factors that support long-term self-renewal, multipotency, and quiescence. We hypothesize that SOX2, OCT4, and NANOG will be enriched in ovarian TICs and may indicate TICs with high relapse potential. We evaluated a panel of eight ovarian cancer cell lines grown in standard 2-D culture or in spheroid-enriching 3-D culture, and correlated expression with growth characteristics, TIC marker expression, and chemotherapy resistance. RNA-sequencing showed that cell cycle regulation pathways involving SOX2 were elevated in 3-D conditions. HGSOC lines had longer doubling-times, greater chemoresistance, and significantly increased expression of SOX2, OCT4, and NANOG in 3-D conditions. CD117+ or ALDH+/CD133+ cells had increased SOX2, OCT4, and NANOG expression. Limiting dilution in in vivo experiments implicated SOX2, but not OCT4 or NANOG, with early tumor-initiation. An analysis of patient data suggested a stronger role for SOX2, relative to OCT4 or NANOG, for tumor relapse potential. Overall, our findings suggest that SOX2 may be a more consistent indicator of ovarian TICs that contribute to tumor repopulation following chemotherapy. Future studies evaluating SOX2 in TIC biology will increase our understanding of the mechanisms that drive ovarian cancer relapse.

scholarly journals Progression-Mediated Changes in Mitochondrial Morphology Promotes Adaptation to Hypoxic Peritoneal Conditions in Serous Ovarian Cancer

2021 ◽  
Vol 10 ◽  
Author(s):  
Joseph P. Grieco ◽  
Mitchell E. Allen ◽  
Justin B. Perry ◽  
Yao Wang ◽  
Yipei Song ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Model ◽  
Gynecological Cancer ◽  
Metastatic Potential ◽  
Adaptation To Hypoxia ◽  
Mitochondrial Morphology ◽  
Serous Ovarian Cancer ◽  
Tumor Initiating Cells ◽  
Mitochondrial Dynamic ◽  
Functional Changes

Ovarian cancer is the deadliest gynecological cancer in women, with a survival rate of less than 30% when the cancer has spread throughout the peritoneal cavity. Aggregation of cancer cells increases their viability and metastatic potential; however, there are limited studies that correlate these functional changes to specific phenotypic alterations. In this study, we investigated changes in mitochondrial morphology and dynamics during malignant transition using our MOSE cell model for progressive serous ovarian cancer. Mitochondrial morphology was changed with increasing malignancy from a filamentous network to single, enlarged organelles due to an imbalance of mitochondrial dynamic proteins (fusion: MFN1/OPA1, fission: DRP1/FIS1). These phenotypic alterations aided the adaptation to hypoxia through the promotion of autophagy and were accompanied by changes in the mitochondrial ultrastructure, mitochondrial membrane potential, and the regulation of reactive oxygen species (ROS) levels. The tumor-initiating cells increased mitochondrial fragmentation after aggregation and exposure to hypoxia that correlated well with our previously observed reduced growth and respiration in spheroids, suggesting that these alterations promote viability in non-permissive conditions. Our identification of such mitochondrial phenotypic changes in malignancy provides a model in which to identify targets for interventions aimed at suppressing metastases.

Is Sphere Assay Useful for the Identification of Cancer Initiating Cells of the Ovary?

2015 ◽  
Vol 25 (1) ◽  
pp. 12-17 ◽  
Author(s):  
María José Martínez-Serrano ◽  
Miguel Caballero-Baños ◽  
Ramon Vilella ◽  
Laura Vidal ◽  
Jaume Pahisa ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Growth Factor Receptor ◽  
Selective Medium ◽  
Current Evidence ◽  
Published Data ◽  
Surface Markers ◽  
Adherent Cells ◽  
Tumor Initiating Cells ◽  
Endothelial Growth Factor

ObjectiveCurrent evidence suggests that the presence of tumor-initiating cells (TICs) in epithelial ovarian cancer (EOC) has a role in chemoresistance and relapse. Surface markers such as CD44+/CD24−, CD117+, and CD133+expression have been reported as potential markers for TICs related to ovarian cancer and tumorigenic cell lines. In this study, we have investigated if spheroid forms are TIC specific or whether they can also be produced by somatic stem cells from healthy tissue in vitro. In addition, we also investigated the specificity of surface markers to identify TICs from papillary serous EOC patients.MethodsCells were obtained from fresh tumors from 10 chemotherapy-naive patients with EOC, and cells from ovarian and tubal epithelium were obtained from 5 healthy menopausal women undergoing surgery for benign pathology and cultured in standard and in selective medium. Cells forming nonadherent spheroids were considered TICs, and the adherent cells were considered as non–TIC-like. Percentages of CD24+, CD44+, CD117+, CD133+, and vascular endothelial growth factor receptor (VEGF-R)+cell surface markers were analyzed by flow cytometry.ResultsFour of 10 EOC cell tissues were excluded from the study. Tumor cells cultured in selective medium developed spheroid forms after 1 to 7 weeks in 5 of 6 EOC patients. No spheroid forms were observed in cultures of cells from healthy women. Unlike previously published data, low levels of CD24+, CD44+, CD117+, and VEGF-R+expression were observed in spheroid cells, whereas expression of CD133+was moderate but higher in adherent cells from papillary serous EOC cells in comparison with adherent cells from controls.ConclusionsPapillary serous EOC contains TICs that form spheroids with low expression of CD44+, CD24+, CD117+and VEGF-R+. Further research is required to find specific surface markers to identify papillary serous TICs.

scholarly journals Characterization of SOX2, OCT4 and NANOG in ovarian cancer tumor-initiating cells

2020 ◽  
Author(s):  
Mikella Robinson ◽  
Samuel F Gilbert ◽  
Jennifer A Waters ◽  
Omar Lujano-Olazaba ◽  
Jacqueline Lara ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Chemotherapy Resistance ◽  
Cancer Cell Lines ◽  
Ovarian Cancer Cells ◽  
Tumor Initiation ◽  
Tumor Initiating Cells ◽  
Ovarian Cancer Cell Lines

AbstractIdentification of tumor initiating cells (TICs) has traditionally relied on expression of surface markers such as CD133, CD44, and CD117 and enzymes such as aldehyde dehydrogenase (ALDH). Unfortunately, these markers are often cell type specific and not reproducible across patient samples. A more reliable indication of TICs may include elevated expression of stem cell transcription factors such as SOX2, OCT4, and NANOG that function to support long-term self-renewal, multipotency, and quiescence. RNA-sequencing studies presented here highlight a potential role for SOX2 in cell cycle progression in cells grown as 3-D spheroids, which are more tumorigenic and contain higher numbers of TICs than their 2-D monolayer cultured counterparts. SOX2, OCT4, and NANOG have not been comprehensively evaluated in ovarian cancer cell lines, although their expression is often associated with tumorigenic cells. We hypothesize that SOX2, OCT4, and NANOG will be enriched in ovarian TICs and will correlate with chemotherapy resistance, tumor initiation, and expression of traditional TIC markers. To investigate this hypothesis, we evaluated SOX2, OCT4, and NANOG in a panel of eight ovarian cancer cell lines grown as a monolayer in standard 2-D culture or as spheroids in TIC-enriching 3-D culture. Our data show that the high-grade serous ovarian cancer (HGSOC) lines CAOV3, CAOV4, OVCAR4, and OVCAR8 had longer doubling-times, greater resistance to chemotherapies, and significantly increased expression of SOX2, OCT4, and NANOG in TIC-enriching 3-D culture conditions. We also found that in vitro chemotherapy treatment enriches for cells with significantly higher expression of SOX2. We further show that the traditional TIC marker, CD117 identifies ovarian cancer cells with enhanced SOX2, OCT4, and NANOG expression. Tumor-initiation studies and analysis of The Cancer Genome Atlas (TCGA) suggest a stronger role for SOX2 in ovarian cancer relapse compared with OCT4 or NANOG. Overall, our study clarifies the expression of SOX2, OCT4, and NANOG in TICs from a variety of ovarian cancer cell lines. Our findings suggest that SOX2 expression is a stronger indicator of ovarian TICs with enhanced tumor-initiation capacity and potential for relapse. Improved identification of ovarian TICs will advance our understanding of TIC biology and facilitate the design of better therapies to eliminate TICs and overcome chemotherapy resistance and disease relapse.

scholarly journals Biomechanical profile of cancer stem-like/tumor-initiating cells derived from a progressive ovarian cancer model

2014 ◽  
Vol 10 (5) ◽  
pp. e1013-e1019 ◽  
Author(s):  
Hesam Babahosseini ◽  
Alperen N. Ketene ◽  
Eva M. Schmelz ◽  
Paul C. Roberts ◽  
Masoud Agah
Keyword(s):  
Ovarian Cancer ◽  
Cancer Model ◽  
Tumor Initiating Cells

Abstract SY35-02: Phenotypic heterogeneity and instability of human serous ovarian cancer tumor-initiating cells

2012 ◽  
Author(s):  
Benjamin G. Neel ◽  
Jocelyn M. Stewart ◽  
Bernd Bodenmiller ◽  
Laurie Ailles ◽  
Craig Gedye ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phenotypic Heterogeneity ◽  
Serous Ovarian Cancer ◽  
Tumor Initiating Cells ◽  
Cancer Tumor

Abstract 4960: Sox2, Oct4, and Nanog expression for identification of ovarian cancer tumor initiating cells

2020 ◽  
Author(s):  
Mikella Robinson ◽  
Samuel F. Gilbert ◽  
Logan J. Alexander ◽  
Samuel E. Green ◽  
Omar Lujano-Olazaba ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Initiating Cells ◽  
Nanog Expression ◽  
Cancer Tumor
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