Surface markers of cancer stem-like cells of ovarian cancer and their clinical relevance

Klemba, Aleksandra; Purzycka-Olewiecka, Joanna Karolina; Wcisło, Gabriel; Czarnecka, Anna M.; Lewicki, Sławomir; Lesyng, Bogdan; Szczylik, Cezary; Kieda, Claudine

doi:10.5114/wo.2018.73885

Cited by 41 publications

(49 citation statements)

References 66 publications

(77 reference statements)

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“…So far, no universal marker combination has been found to faithfully indicate ovarian cancer stem-like cells (CSLC), although surface proteins CD44 and CD133 are proposed by several authors (reviewed in: [ 24 , 25 ]). Flow cytometry (FC) detection of CD44 and CD133 showed that the majority of ovarian cancer lines tested contained approximately 0.1% of CD44+/CD133+ cells (putative CSLC).…”

Section: Resultsmentioning

confidence: 99%

Establishment and Characterization of the Novel High-Grade Serous Ovarian Cancer Cell Line OVPA8

Tudrej

Olbryt

Zembala‐Nożyńska

et al. 2018

IJMS

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High-grade serous ovarian carcinoma (HGSOC) is the most frequent histological type of ovarian cancer and the one with worst prognosis. Unfortunately, the majority of established ovarian cancer cell lines which are used in the research have unclear histological origin and probably do not represent HGSOC. Thus, new and reliable models of HGSOC are needed. Ascitic fluid from a patient with recurrent HGSOC was used to establish a stable cancer cell line. Cells were characterized by cytogenetic karyotyping and short tandem repeat (STR) profiling. New generation sequencing was applied to test for hot-spot mutations in 50 cancer-associated genes and fluorescence in situ hybridization (FISH) analysis was used to check for TP53 status. Cells were analyzed for expression of several marker genes/proteins by reverse-transcription polymerase chain reaction (RT-PCR), fluorescence-activated cell sorting (FACS), and immunocytochemistry (ICC). Functional tests were performed to compare OVPA8 cells with five commercially available and frequently used ovarian cancer cell lines: SKOV3, A2780, OVCAR3, ES2, and OAW42. Our newly-established OVPA8 cell line shows morphologic and genetic features consistent with HGSOC, such as epithelial morphology, multiple chromosomal aberrations, TP53 mutation, BRCA1 mutation, and loss of one copy of BRCA2. The OVPA8 line has a stable STR profile. Cells are positive for EpCAM, CK19, and CD44; they have relatively low plating efficiency/ability to form spheroids, a low migration rate, and intermediate invasiveness in matrigel, as compared to other ovarian cancer lines. OVPA8 is sensitive to paclitaxel and resistant to cisplatin. We also tested two FGFR inhibitors; OVPA8 cells were resistant to AZD4547 (AstraZeneca, London, UK), but sensitive to the new inhibitor CPL304-110-01 (Celon Pharma, Łomianki/Kiełpin, Poland). We have established and characterized a novel cell line, OVPA8, which can be a valuable preclinical model for studies on high-grade serous ovarian cancer.

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Section: Resultsmentioning

confidence: 99%

Establishment and Characterization of the Novel High-Grade Serous Ovarian Cancer Cell Line OVPA8

Tudrej

Olbryt

Zembala‐Nożyńska

et al. 2018

IJMS

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“…is commonly used as a stem cell marker in combination with CD117, MyD88, E-cadherin/CD34, and CD24/EpCAM. Each of these CD44 + cell populations has been demonstrated to have stem-like properties (reviewed in Klemba et al) 78 . In conclusion there are multiple surface markers used to identify CSCs in ovarian cancer.…”

Section: Cell Surface Markersmentioning

confidence: 99%

Can Stemness and Chemoresistance be Therapeutically Targeted via Signaling Pathways in Ovarian Cancer?

Roy

Dahl²

2018

Preprint

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Ovarian cancer is the most lethal gynecological malignancy. Poor overall survival, particularly for patients with high grade serous (HGS) ovarian cancer, are often attributed to late stage at diagnosis and relapse following chemotherapy. HGS ovarian cancer is a heterogenous disease in that few genes are consistently mutated between patients. Additionally, HGS ovarian cancer is characterized by high genomic instability. For these reasons personalized approaches may be necessary for effective treatment and cure. Understanding the molecular mechanisms that contribute to tumor metastasis and chemoresistance are essential to improve survival rates. One favored model for tumor metastasis and chemoresistance is the cancer stem cell (CSC) model. CSCs are cells with enhanced self-renewal properties that are enriched following chemotherapy. Elimination of this cell population is thought to be a mechanism to increase therapeutic response. Therefore, accurate identification of stem cell populations that are most clinically relevant is necessary. While many CSC identifiers (ALDH, OCT4, CD133, and side population) have been established, it is still not clear which population(s) will be most beneficial to targeted in patients. Therefore, there is a critical need to characterize CSCs with reliable markers and find their weaknesses that will make the CSCs amenable to therapy. Many signaling pathways are implicated for their roles in CSC initiation and maintenance. Therapeutically targeting pathways needed for CSC initiation or maintenance may be an effective way of treating HGS ovarian cancer patients. In conclusion, the prognosis for HGS ovarian cancer may be improved by combining CSC phenotyping with targeted therapies for pathways involved in CSC maintenance.

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“…Cluster 6 highly expressed vimentin and Ki-67 along with comparatively lower expression of EMT markers (ZEB1 and ZEB2), suggestive of cells undergoing mesenchymal to epithelial transition (Figure 3E). Ovarian cancer stem cells marked by co-expression of CD33, CD44, CD117 and CD24 expression were not observed 32 . Cells in this cluster expressed IL-6 which correlates with poor prognosis in ovarian cancer and TGF-β which induces an aggressive cancer phenotype 33–36 .…”

Section: Resultsmentioning

confidence: 95%

Characterizing the tumor microenvironment of metastatic ovarian cancer by single cell transcriptomics

Olalekan

Xie

Back

et al. 2020

Preprint

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45Epithelial ovarian cancer is a highly heterogenous, metastatic and lethal disease. The presence 46 of CD8 + T cells within ovarian tumors is positively associated with overall patient survival. 47Determining if a patient has T cells that respond to immunotherapies, their characteristics and 48 how they can be manipulated to target cancer cells is an area of intense investigation in cancer 49therapy. This study determines the cellular composition and the transcriptional state of immune 50 cells in metastatic ovarian cancer samples from patients using single cell RNA sequencing (scRNA-51 seq). Hierarchical clustering stratified our patient cohort into 2 main groups: 1) a high T cell 52 infiltration (high Tinf) group and 2) a low T cell infiltration (low Tinf) group. To assess the immune 53 response in these patient samples, we performed an unsupervised clustering of the T cell 54 population in each group. The T cell population clustered into 4 and 3 subpopulations in the high 55Tinf T cell and low Tinf respectively. A granulysin expressing T cell cluster was identified and unique 56 to the High Tinf group. Interestingly, although both groups had resident memory CD8 + T (CD8 + Trm) 57 cells, only the CD8 + Trm cells in the high Tinf group expressed TOX, a recently described 58 transcription factor. TOX confers longevity to T cells within immunosuppressive environment 59 such as cancer. Interestingly, along with TOX + T cells, we found a unique plasmablast cluster and 60 an IRF8 + macrophage cluster unique to the high Tinf group. Our comprehensive scRNA-seq study 61 provides important insights in elucidating the immune response in ovarian cancer patients.

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Surface markers of cancer stem-like cells of ovarian cancer and their clinical relevance

Cited by 41 publications

References 66 publications

Establishment and Characterization of the Novel High-Grade Serous Ovarian Cancer Cell Line OVPA8

Establishment and Characterization of the Novel High-Grade Serous Ovarian Cancer Cell Line OVPA8

Can Stemness and Chemoresistance be Therapeutically Targeted via Signaling Pathways in Ovarian Cancer?

Characterizing the tumor microenvironment of metastatic ovarian cancer by single cell transcriptomics

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