Role of CXCL10 in angiogenesis of renal cell carcinoma

Abstract

Angiogenic process is complex and several factors are involved as a promoter or inhibitor in angiogenesis. Tumor can use the imbalance of pro- and antiangiogenic factors in progression. The CXC chemokine family is consisted of pro- or antiangiogenic factors. Recent studies revealed C-X-C motif chemokine 10 (CXCL10) as an anti-angiogenic factor in response to angiogenic factors like bFGF or VEGF. However, a role of CXCL10 in cancer and angiogenesis is unclear. Here, we investigated the role of CXCL10 on tumor angiogenesis and its mechanisms in renal cell carcinoma. CXCL10 inhibited proliferation and tube formation of HUVEC in a dose-dependent manner, while it did not affect in vitro tumor proliferation of renal cell carcinoma cells. Expression of CXCL10 was down-regulated in Caki-1, UMRC3 and UMRC6 cells. Overexpression of CXCL10 suppressed expression of angiogenic factors including HIF-1α, EGF, VEGFB, VEGFC, HGF, and MMP9 in Caki-1 cells. In vivo, restoration of CXCL10 expression suppresses tumor growth in renal cell carcinoma by suppressing tumor angiogenesis in xenografts. Our data suggest that targeting CXCL10 is a novel therapeutic option in renal cell carcinoma.