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?-hCG promotes epithelial ovarian cancer metastasis through ERK/MMP2 signaling pathway.

ABSTRACT: Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy, with typically extensive intraperitoneal implantation leading to poor prognosis. Our previous study preliminarily demonstrated ?-hCG can promote tumorigenesis in immortalized nontumorigenic ovarian epithelial cells. In this study, the roles and mechanisms of ?-hCG in regulating EOC proliferation and metastasis were thoroughly explored. First, histologically, ?-hCG was aberrantly overexpressed in human EOC metastatic tissues, and significantly correlated with FIGO stage, tumor size, differentiation, histologic grade and high grade serous ovarian carcinoma (HGSOC) (P < 0.05). However, serologically, ?-hCG expression showed no significant difference between EOC and nonmalignant ovarian patients. Second, ?-hCG was confirmed to have no significant effects on EOC proliferation in vitro and in vivo, while ?-hCG upregulation was proven to promote migration and invasion ability in ES-2 and OVCAR-3 cells in vitro (P < 0.05), and ?-hCG downregulation in SKOV3 cells had the opposite effect. Moreover, more invadopodia protrusions, mitochondria accumulations and cytoskeletal rearrangements were observed in ?-hCG-overexpressing ES-2 cells, while ?-hCG-depleted SKOV3 cells produced the opposite effect. Furthermore, ?-hCG was confirmed to clearly facilitate intraperitoneal metastasis in nude mouse orthotopic ovarian xenograft models. Importantly, these effects of ?-hCG were mediated by activation of the ERK/MMP2 signaling pathway, independently of luteinizing hormone/chorionic gonadotropin receptor (LHCGR) presence, and inhibition the pathway with the p-ERK1/2 inhibitor SCH772984 significantly impaired the tumor-promoting effects induced by ?-hCG. Collectively, these data provide new insight into the roles and mechanisms of ?-hCG in regulating EOC metastasis through ERK/MMP2 signaling pathway and may become a new target for therapeutic intervention.

SUBMITTER: Wu W

PROVIDER: S-EPMC6343691 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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β-hCG promotes epithelial ovarian cancer metastasis through ERK/MMP2 signaling pathway.

Wu Weimin W Gao Hao H Li Xiaofeng X Peng Shumin S Yu Jing J Liu Na N Zhan Guangxi G Zhu Yong Y Wang Kai K Guo Xiaoqing X

Cell cycle (Georgetown, Tex.) 20181224 1

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy, with typically extensive intraperitoneal implantation leading to poor prognosis. Our previous study preliminarily demonstrated β-hCG can promote tumorigenesis in immortalized nontumorigenic ovarian epithelial cells. In this study, the roles and mechanisms of β-hCG in regulating EOC proliferation and metastasis were thoroughly explored. First, histologically, β-hCG was aberrantly overexpressed in human EOC metastatic tissu ...[more]

PMID: 30582718

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?-hCG promotes epithelial ovarian cancer metastasis through ERK/MMP2 signaling pathway.

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β-hCG promotes epithelial ovarian cancer metastasis through ERK/MMP2 signaling pathway.

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