Cervical carcinoma cells stimulate the angiogenesis through TSLP promoting growth and activation of vascular endothelial cells

Abstract

Problem: To explore whether cervical carcinomas cells-derived thymic stromal lymphopoietin (TSLP) modulates the biologic behavior of vascular endothelial cells and herein participates in the angiogenesis in the cervical cancer pathogenesis.

Method of study: We analyzed expression of TSLP and its receptor (TSLPR) in cervical cancer cells by immunohistochemistry, ELISA, and flow cytometry, respectively. We further investigated the effects of TSLP on the proliferation, apoptosis, activation, and angiogenesis in vitro of human umbilical vein endothelial cells (HUVECs).

Results: It has been found that the cervical cancer cells translate TSLP and endothelial cells express TSLPR in cervical cancer tissues. Both HeLa and CaSki cells secret TSLP in a time-dependent manner, and the ratio of TSLPR-positive HUVECs is about 30%. It has been showed that recombinant human TSLP (rhTSLP) can significantly increase Ki67 and CD62E expression in HUVECs and interleukin-6 (IL-6) levels from HeLa and CaSki cells; on the contrary, anti-human TSLP or TSLPR neutralizing antibody down-regulates the expression of Ki67, angiogenesis-relative molecules CD62E, and CD105 in HUVECs cocultured with HeLa or CasKi cells and inhibits IL-6 secretion from HeLa and CaSki cells. Moreover, both rhTSLP and endogenous TSLP from HeLa or CaSki cells obviously stimulate the proliferation, activation, and angiogenesis, but not influence the apoptosis of HUVECs in vitro.

Conclusion: This study has demonstrated that TSLP secreted by cervical carcinomas cells is involved in the angiogenesis of cervical cancer in a paracrine manner.