The Crosstalk Between Cervical Carcinoma Cells And Vascular Endothelial Cells Mediated By IL-27 Restrains Angiogensis In Vitro

Purpose: To explore whether cervical carcinomas cells-derived interleukin-27(IL-27)modulates the biological behavior of vascular endothelial cells and herein participates in the angiogenesis.Methods: The expression of IL-27 in cervical cancer tissues and cervical cell lines(HeLa and Ca Ski cells)was analyzed by immunohistochemistry,ELISA and flow cytometry,respectively.Then,the effects of overexpression of IL-27 on the proliferation and apoptosis-related molecules,and angiogenesis in vitro of human umbilical vein endothelial cells(HUVECs)were investigated.Finally,in vivo experiment was performed to further confirm.Results: Compared with cervicitis,the cervical cancer tissues highly expressed IL-27.Both He La and Ca Ski cells secreted IL-27,and HUVECs expressed low levels of IL-27 receptors(IL-27R: WSX-1 and gp130).However,the co-culture of cervical cell lines and HUVECs led to a significant elevation of IL-27 R on HUVECs and IL-27+He La cells,but a decreased level of IL-27+Cas Ki cells.Co-culturing with IL-27-overexpressed He La cells down-regulated Ki-67 and Bcl-2,and up-regulated Fas expression in HUVECs.In addition,overexpression of IL-27 in He La cells and Cas Ki cells secreted less IL-8 compared with control cells,and could further restricts angiogenesis in vitro.In the subcutaneous tumorous model of C57/BL6 mouse,there were decreased vessel density and tumor volume when inoculation with lentivral-IL-27-tranfected TC-1 cells.Conclusion: This study indicates that IL-27 secreted by cervical carcinomas cells restricts the angiogenesis in a paracrine manner in the pathogenesis of cervical cancer.