Characterization of stem cell and cancer stem cell populations in ovary and ovarian tumors

Abstract

BackgroundOvarian cancer is a complicated malady associated with cancer stem cells (CSCs) contributing to 238,700 estimated new cases and 151,900 deaths per year, worldwide. CSCs comprise a tiny fraction of tumor-bulk responsible for cancer recurrence and eventual mortality. CSCs or tumor initiating cells are responsible for self-renewal, differentiation and proliferative potential, tumor initiation capability, its progression, drug resistance and metastatic spread. Although several biomarkers are implicated in these processes, their distribution within the ovary and association with single cell type has neither been established nor demonstrated across ovarian tumor developmental stages. Therefore, precise identification, thorough characterization and effective targeted destruction of dormant and highly proliferating potent CSC populations is an immediate need.ResultsIn view of this, distribution of various CSC (ALDH1/2, C-KIT, CD133, CD24 and CD44) and cell proliferation (KI67) specific markers in the ovarian surface epithelium (OSE) and cortex regions in normal ovary, and benign, borderline and high grade metastatic ovarian tumors by immuno-histochemistry and confocal microscopy was studied. We further confirmed their expression by RT-PCR analysis. Co-expression analysis of stem cell (OCT4, SSEA4) and CSC (ALDH1/2, CD44 and LGR5) markers with proliferation marker (KI67) in HG tumors revealed dual positive proliferating stem and CSCs, few non-proliferating stem/CSC (SSEA4+/KI67− and ALDH1/2+/KI67−) and only KI67+ cells in cortex, signifying dynamic populations and interesting cellular hierarchy in cortex region. Smaller spherical (≤ 5 μm) and larger spindle/elliptical shaped (~ 10 μm) cell populations with high nucleo-cytoplasmic ratio were detected across all samples (including normal ovaries) but with variable distribution and characteristic stage-wise marker expression across different tumor stages.ConclusionsDiverse stem and CSC populations expressing characteristic markers revealing distinct phenotypes (spherical ≤5 μm and spindle/elliptical ~ 10 μm) were distributed within different tumor stages studied signifying dynamic and probable functional hierarchy within these cell types. Involvement of extra-ovarian sites of origin of stem and CSCs requires rigorous evaluation. Quantitative analysis of potent CSC populations, their mechanisms and pathways for self-renewal, chemo-resistance, metastatic spread etc. with respect to various markers studied, will provide better insights and targets for developing effective therapeutics to prevent metastasis and eventually help improve patient mortality.Electronic supplementary materialThe online version of this article (10.1186/s13048-018-0439-3) contains supplementary material, which is available to authorized users.

A natural compound obtained from Valeriana�jatamansi selectively inhibits glioma stem cells

“…S2. The 1 H-NMR and 13 C-NMR data of Rupesin E are as follows and consistent to those of the references (33)(34)(35)(36).…”

“…Since cancer stem cells, known as tumor-initiating cells (TICs), were first identified in acute myelogenous leukemia (10), tumor stem cells have become a hotspot of research. In numerous types of tumor tissues, such as myeloma, lung cancer and ovarian cancer, a small number of cells have the ability of self-renewal, infinite proliferation and multidirectional differentiation, with the basic characteristics of stem cells, known as tumor stem cells (11)(12)(13). They maintain the growth and proliferation of the tumor (14)(15)(16).…”

Histone demethylase KDM4C is required for ovarian cancer stem cell maintenance

“…Western Blot results showed that KDM4C protein level was increased in SK-OV-3 and HO-8910 sphere when compared with monolayer culture ( Figure 1D). Consistent with previous reports, stem cells factor OCT4 was also enriched in these CSCs ( Figure 1D) [18].…”

Antitumoral Effects of Metformin in Ovarian Cancer

“…The cancer stem cells, recently called "tumor-initiating cells," are a tumoral cell subpopulation with critical role in therapy resistance and metastasis [103][104][105]. There are several markers to identify them, as lactate dehydrogenase (LDH), aldehyde dehydrogenase (ALDH), or cell-surface antigens as CD44, CD133, or CD117 [106][107][108]. Metformin treatment decreases the abundance of ovarian cancer LDH+ and decreases its ability to form tumor spheres, an attachment-independent growth characteristic of these kinds of cells [109].…”