Xu Jiao, Zheng Tuochen, Hong Wenli, Ye Haifeng, Hu Chuan, Zheng Yuehui
Jiangxi Medical College, Nanchang University, Nanchang, China.
The Key Laboratory of Reproductive Physiology and Pathology of Jiangxi Provincial, Nanchang, China.
Cell Physiol Biochem. 2018;50(1):214-232. doi: 10.1159/000494001. Epub 2018 Oct 18.
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.
卵巢被一层中胚层来源的白色卵巢表面上皮（OSE）所包围，该上皮衬于胚内体腔，由单层扁平至立方形再到低假复层柱状上皮细胞组成。其完整性通过简单的桥粒、不完全紧密连接、多种整合素和钙黏蛋白得以维持。最近的研究发现，卵巢干细胞（OSCs）存在于OSE内，可能在成年期负责新卵泡生成和卵巢癌的发生。决定OSCs是进行新卵泡生成还是引发卵巢癌的因素，是研究人员和临床医生极为感兴趣的。越来越多的证据表明，卵巢表面上皮干细胞决定进行新卵泡生成或发生卵巢癌转化的机制可能包括内部和外部因素。在此，我们综述了近期关于内部因素的研究进展，包括基因、信号通路和长链非编码RNA：OSE干细胞如何通过p53、KRAS、BRAF和PTEN等各种基因以及PIK3CA中的突变，并通过各种信号通路，包括转化生长因子-β（TGF-B）通路、Wnt信号通路、Notch信号通路、核因子-κB信号转导子和转录激活子3（STAT3）通路以及Hedgehog（HH）通路，介导卵巢癌的发生和发展。与正常卵巢组织和细胞系相比，上皮性卵巢癌组织和细胞系中一系列长链非编码RNA的表达发生了变化。以及外部因素，包括持续排卵、促性腺激素和慢性炎症：频繁排卵且无长期休眠会增加患病风险，因为排卵部位反复破裂和修复为遗传异常的积累提供了机会；促卵泡生成素（FSH）通过诱导血管内皮生长因子A（VEGFA，VEGF）表达增加来支持肿瘤生长、促进血管生成，并可能改变某些致癌途径，从而影响卵巢癌转移的各个方面，如抑制细胞凋亡，进而促进增殖和侵袭性表型；炎症有助于肿瘤发生，这有助于确定OSCs是进行新卵泡生成还是发生卵巢肿瘤形成。了解这个问题对于开发针对卵巢早衰和卵巢癌预防及治疗的新策略至关重要。
