Mechanism for the Decision of Ovarian Surface Epithelial Stem Cells to Undergo Neo-Oogenesis or Ovarian Tumorigenesis

Abstract

The ovary is surrounded by a whitish layer of mesodermally derived ovarian surface epithelium (OSE) that lines the intraembryonic celom and comprises simple squamous to cuboidal to low pseudostratified columnar epithelial cells. Its integrity is maintained by simple desmosomes, incomplete tight junctions, several integrins and cadherins. Recent research has found that ovarian stem cells (OSCs) exist within the OSE and may be responsible for both neo-oogenesis and ovarian cancer during adult life. The factors determining whether OSCs undergo neo-oogenesis or ovarian cancer are of great interest to researchers and clinicians. Accumulating evidence suggests the mechanism for the decision of ovarian surface epithelial stem cells to undergo either neo-oogenesis or ovarian cancer transformation may comprise both internal and external factors. Here, we review recent progress on how the internal factors, including genes, signaling pathways and lncRNA: OSE stem cells mediate the development and progression of ovarian cancer through various genes such as p53, KRAS, BRAF, and PTEN, and mutations in PIK3CA, and through various signaling pathways, including TGF-B pathway, Wnt signaling pathway, Notch signaling pathway, NF-kB signal transducer and transcriptional activator 3 (STAT3) pathway and Hedghog (HH) pathway. A series of expressions of IncRNA have changed in epithelial ovarian cancer tissues and cell lines compared to normal ovarian tissues and cell lines. As well as external factors, including incessant ovulation, gonadotropin and chronicinflammation: Frequent ovulation, without long-term dormancy, increases the risk of illness, because repeated rupture and repair at the ovulation site provides an opportunity for the accumulation of genetic aberrations; FSH affects all aspects of ovarian cancer metastasis, such as inhibition of apoptosis, through Induction of increased expression of VEGFA (VEGF) to support tumor growth, promote vascular growth, and possibly alter certain oncogenic pathways, thereby promoting proliferation and invasive phenotypic inflammation contributes to tumorigenesis, which help determine whether OSCs undergo neo-oogenesis or ovarian tumorigenesis. Understanding this issue is critical for developing novel strategies for premature ovarian failure and ovarian cancer prevention and therapy.

The ovarian stroma as a new frontier

“…1 and Table 1). The keratin-rich ovarian surface epithelial cell layer helps to facilitate repair after ovulation and dynamically expands and contracts with cyclic ovarian changes (Xu et al 2018, Hartanti et al 2020. Scanning electron microscopy and immunofluorescence of the surface epithelium of developing fetal bovine ovaries demonstrated expansion from the hilar region to…”

Factors in Oncogenesis: Viral Infections in Ovarian Cancer

“…The main risk factors for HGSOC are the lifetime number of ovulations: the ovary can be confronted with carcinogenesis if the number of lifetime ovulations correlates with an increased risk of OC [21]. Ovulation promotes the migration and adhesion of malignant cells to the ovary by disrupting the OSE, as well as releasing chemokines and cytokines [22]. The wound thus formed is repaired by the proliferation of the epithelial cells and such aggregation forms inclusion cysts, which have the potential to trigger ovarian carcinogenesis [15,18,23,24].…”

Melatonin is a potential inhibitor of ovarian cancer: molecular aspects

“…Therefore, there is a serious require for finding, and developing new effect therapeutic platforms combining anti-angiogenic therapies along with conventional cytoreductive treatments in the management of different cancers [83]. Vascular endothelial growth factor (VEGF) is significantly over-expresses in cancer patients [85, 86] VEGF inhibits apoptosis, protects tumor and vascular growth, and enhances proliferation and inflammation leading to carcinogenesis [87]. Melatonin decreases VEGF secretion resulting in inhibition of angiogenesis in tumors [88].…”