The cross talk between cervical carcinoma cells and vascular endothelial cells mediated by IL‐27 restrains angiogenesis

Problem To explore whether cervical carcinoma cell‐derived interleukin‐27 ( IL ‐27) modulates the angiogenesis of vascular endothelial cells. Method of study The expression of IL ‐27 in cervical cancer tissues and cervical cell lines was analyzed by immunohistochemistry, ELISA and flow cytometry. Then, the effects of IL ‐27 on the proliferation and apoptosis‐related molecules and angiogenesis in vitro of human umbilical vein endothelial cells ( HUVEC s) were investigated. Finally, in vivo experiment was performed to further confirm the effects of IL‐27. Results Compared with cervicitis, the cervical cancer tissues highly expressed IL ‐27. Both HeLa and CaSki cells secreted IL ‐27, and HUVEC s expressed low levels of IL ‐27 receptors ( IL ‐27R). However, the co‐culture of cervical cell lines and HUVEC s led to a significant elevation of IL ‐27R on HUVEC s. Co‐culturing with IL ‐27‐overexpressed HeLa cells downregulated Ki‐67 and Bcl‐2 and upregulated Fas expression in HUVEC s. In addition, overexpression of IL ‐27 in HeLa cells and CasKi cells secreted less IL ‐8 and could further restrict angiogenesis compared with control cells in vitro. In the subcutaneous tumorous model of C57/ BL 6 mouse, there were decreased vessel density and tumor volume when inoculation with IL ‐27‐overexpressed TC ‐1 cells. Conclusion This study indicates that IL ‐27 secreted by cervical carcinoma cells restricts the angiogenesis in a paracrine manner in the pathogenesis of cervical cancer.