Abstract: Background and purpose: Semaphorin 3A (Sema3A) is initially considered to play an important role in axonal orientation. Recently, Sema3A has also been considered as a candidate tumor suppressor involved in the tumorigenesis. The purpose of this study was to investigate the relationship between Sema3A and metastasis of epithelial ovarian cancer (EOC) and its underlying mechanism. Methods: We selected 20 ovarian tissue samples of EOC patients with peritoneal metastasis (the metastatic group) and 20 ovarian tissue samples of EOC patients without peritoneal metastasis (the non-metastatic group) treated initially in the Department of Gynecology of Shanghai Fifth People’s Hospital, Fudan University from Mar. 2018 to Dec. 2018, and the expression of Sema3A in ovarian tissue samples of two groups was detected by immunohistochemistry. The relationship between Sema3A and the clinical pathological features of each group was analyzed. The expression levels of Sema3A in five ovarian cancer cell lines were detected by Western blot and real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR). Establishment of stable ovarian cancer cell lines harboring Sema3A cDNA or shRNA was conducted by lentilviral infection. Transwell method and scratch test were employed to determine the invasion and migration abilities in two cell lines. The expressions of epithelial-mesenchymal transition (EMT) markers and matrix metalloproteinase (MMP)-2 protein in two cell lines were detected by Western blot. Results: The expression level of Sema3A in the metastatic group was significantly lower than that in the non-metastatic group. In the metastatic group, the expression of Sema3A was not related to the patient's age, degree of tissue differentiation or tumor size, but related to pathological type, International Federation of Gynecology and Obstetrics (FIGO) stage and lymph node metastasis. Among the five ovarian cancer cell lines, the expression level of Sema3A was lower in A2780 cells, but higher in Skov3 cells. Overexpression of Sema3A inhibited the migration and invasion abilities in A2780. Meanwhile, levels of E-cadherin and ZO-1 were significantly up-regulated, and levels of N-cadherin, Slug and MMP-2 were significantly down-regulated. Knockdown of Sema3A promoted the migration and invasion abilities in SK-OV-3. Meanwhile, levels of E-cadherin and ZO-1 were significantly down-regulated whereas levels of N-cadherin, Slug and MMP-2 were significantly up-regulated. Conclusion: Sema3A participates in the metastasis of EOC by regulating EMT/MMP-2, and may be used as a biological indicator to predict metastasis and prognosis of EOC.

Key words: Epithelial ovarian cancer, Sema3A, Peritoneal metastasis, Epithelial-mesenchymal transition, Matrix metalloproteinase