Impact of the putative cancer stem cell markers and growth factor receptor expression on the sensitivity of ovarian cancer cells to treatment with various forms of small molecule tyrosine kinase inhibitors and cytotoxic drugs

AbstractHigh-grade serous ovarian cancer (HGSOC) is the most lethal gynecological malignancy that is primarily detected at the metastatic stage. Most HGSOC originates from the fallopian tube epithelium (FTE) and metastasizes to the ovary before invading the peritoneum; therefore, it is crucial to study disease initiation and progression using FTE-derived models. We previously demonstrated that loss of PTEN from the FTE leads to ovarian cancer. In the present study, loss of PTEN in FTE led to the enrichment of cancer stem cell markers such as LGR5, WNT4, ALDH1, CD44. Interestingly, loss of the transcription factor PAX2, which is a common and early alteration in HGSOC, played a pivotal role in the expression of cancer stem-like cells (CSC) markers and cell function. In addition, loss of PTEN led to the generation of two distinct subpopulations of cells with different CSC marker expression, tumorigenicity, and chemoresistance profiles. Taken together, these data suggest that loss of PTEN induces reprogramming of the FTE cells into a more stem-like phenotype due to loss of PAX2 and provides a model to study early events during the FTE-driven ovarian cancer tumor formation.

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Expression of cancer stem cell markers CD44, CD133, and ALDH in a primary tumor before and after platinum-containing chemotherapy in ovarian cancer

CLINICAL AND EXPERIMENTAL MORPHOLOGY ◽

10.31088/cem2021.10.4.63-71 ◽

2021 ◽

Vol 10 (4) ◽

pp. 63-71

Author(s):

S.O. Gening ◽

◽

I.I. Antoneeva ◽

T.V. Abakumova ◽

T.P. Gening ◽

...

Keyword(s):

Ovarian Cancer ◽

Stem Cells ◽

Stem Cell ◽

Neoadjuvant Chemotherapy ◽

Cancer Stem Cell ◽

Primary Tumor ◽

Stem Cell Markers ◽

Tissue Samples ◽

Cancer Stem Cell Markers ◽

Platinum Sensitive

Introduction. Ovarian cancer (OC) is characterized by an unfavorable clinical course. Difficulties in the treatment of OC can be due to intratumoral heterogeneity, which includes the presence of stem cells. The aim of this study was to assess the expression of stem markers in the tissue of primary OC before and during chemotherapy of OC in association with the clinical features of the disease. Materials and methods. A retrospective study evaluated tissue samples of the primary tumors of patients (n=28) with stages I–IV epithelial OC obtained before or after 3 courses of chemotherapy. The expression of ALDH, CD44, and CD133 was assessed by immunohistochemistry. Results. In samples of high-grade serous adenocarcinoma, the percentages of cells expressing ALDH (p=0.008), CD44 (p=0.026), and CD133 (p=0.059) were lower than in other subtypes. Tissue samples obtained before treatment showed a higher percentage of cells expressing CD44 (p=0.053) than the ones obtained after neoadjuvant chemotherapy. There was a tendency towards higher expression of CD44 (p=0.056) and ALDH (p=0.074) in stages I–II tumors when compared to that in stages III–IV. In the neoadjuvant chemotherapy group, patients with clinically platinum-sensitive tumors had a higher percentage of CD44+ cells than those with non-platinum-sensitive ones (p=0.038). The number of tumor cells expressing ALDH rose with the increase in CD44+ cells number (R2=0.280, p=0.005). We found a positive correlation between the numbers of CD44+ and CD133+ cells in the tumor parenchyma (r=0.408, p=0.031). Conclusion. Cancer stem cell markers are co-expressed in primary tumor tissue in OC. The expression of stem markers differs depending on the histological subtype and the presence of prior exposure to chemotherapy. Keywords: tumor stem cells, ovarian cancer, chemotherapy, CD44, CD133, ALDH, immunohistochemistry

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