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Downregulation or absent of TNFSF15 in Ovarian Cancer Is a Pre-requisite for Tumor Neovascularization

  

  • Received:2011-10-31 Revised:2012-02-08 Published:2012-09-15 Online:2012-09-15

Abstract: Abstract Objective: To study the expression of tumor necrosis factor superfamily-15 (TNFSF15) in human ovarian cancer specimens, and it’s relationship with the clinical staging. Furthermore, we mean to study the effects of TNFSF15 on tumor angiogenesis and growth in vivo. Methods: The expression of TNFSF15 in ovary tissue specimens (12 normal and 94 ovarian cancer) were detected by immunohistochemistry assay. We used recombinant TNFSF15 to treat ID8-bearing C57BL/6 mice via intraperitoneal injection or used TNFSF15-shRNA to knock down its expression in tumor microenvironment, and then the influences on tumor angiogenesis and growth were assessed. Results:Compared to the normal ovary tissues, the expression of TNFSF15 was low or absent in the cancer specimens(P<0.001)and TNFSF15 levels are inversely correlated to the clinical stages of human ovarian cancer(P<0.005). Using a mouse syngeneic tumor model, we demonstrated that recombinantNFSF15 markedly inhibited the growth of ID8 tumors(P<0.05); on the other hand, TNFSF15-shRNAadministration could accelerate the growth of ID8 tumors(P<0.05). Conclusion: TNFSF15 downregulation or absent in ovarian cancer microenvironment is a pre-requisite for tumor neovascularization and tumor growth.

Key words: ovarian cancer, tumor, neovascularization, ID8 cell lines