CCL4 promotes the cell proliferation, invasion and migration of endometrial carcinoma by targeting the VEGF-A signal pathway

Int J Clin Exp Pathol. 2017 Nov 1;10(11):11288-11299. eCollection 2017.

Abstract

Chemokine (C-C motif) ligand 4 (CCL4) and vascular endothelial growth factor-A (VEGF-A) are involved in the progression and metastasis of some tumors, including ovarian cancer, colon cancer and prostate cancer. However, the roles of CCL4 and VEGF-A in human endometrial cancer (EC) are still unclear. Here, we demonstrated that the production of CCL4 and VEGF-A was significantly higher in EC tissues than in normal tissues, and their expression profiles were associated with the clinical stage of EC. In addition, we found that CCL4 promoted the angiogenesis and invasive ability of EC tumors by increasing the production of VEGF-A. We further confirmed the effect of CCL4 in the growth of EC tumors by silencing the expression of CCL4 in EC cell lines. Finally, we found that CCL4 upregulated VEGF-A expression by activating STAT3, and it enhanced the progression and metastasis of EC. Our study showed that CCL4 promoted tumor growth by upregulating VEGF-A expression, which affected the STAT3 signal pathway in the EC cells.

Keywords: CCL4; Endometrial cancer; STAT3; VEGF-A.