Abstract B18: CXCL10 suppresses tumor angiogenesis and impedes expression of critical angiogenic factors in renal cell carcinoma

Abstract

Abstract Background: Angiogenic progress is complex and several factors are involved as a promoter or inhibitor of angiogenesis. Tumor can use the imbalance of pro- and antiangiogenic factors in progression. The CXC chemokine family are consisted of pro- or antiangiogenic factors. Recent studies revealed 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. Methods: Human vascular endothelial cell (HUVEC) was used to evaluate the effects of CXCL10 on endothelial cells. MTS assay was performed to assess cell proliferation. Cell cycle analysis was performed using flow cytometry with propidium iodide. RT-PCR and western blot were performed to assess the baseline expression of CXCL10 in a panel of renal cell carcinoma cells. Overexpression of CXCL10 was developed by lentiviral transfection. Quantitative RT-PCR for angiogenic factors (VEGF, PDGF, FGF, MMP9) was performed by angiogenesis multigene screening array. Subcutaneous tumor xenografts were developed using Caki-1 cells to evaluate in vivo effects of CXCL10. Results: 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 downregulated in Caki-1, UMRC3 and UMRC6 cells. Overexpression of CXCL10 suppressed expression of angiogenic factors including VEGF-A, PDGF, FGF2 and MMP9 in Caki-1 cells, suggesting that CXCL10 is involved non only as an anti-angiogenic factor but also as a suppressor of critical angiogenic factors in renal cell carcinoma. In vivo Restoration of CXCL10 expression suppresses tumor growth in renal cell carcinoma by suppressing tumor angiogenesis in xenografts. Conclusions: CXCL10 has a role as an anti-angiogenic factor and also as a suppressor of critical angiogenic factors in renal cell carcinoma. Restoration of CXCL10 expression suppresses tumor growth in renal cell carcinoma by impeding expression of other angiogenic factors including VEGF, PDGF, FGF, MMP9 in renal cell carcinoma as well as inducing anti-angiogenic effect on endothelial cells. Our data suggest that targeting CXCL10 might be a novel therapeutic option for advanced renal cell carcinoma. Citation Format: Hyun A Jin, Jun Hyeok Heo, You Hyun Kang, Ki Hong Kim, Kyung Suk Han, Sung Joon Hong. CXCL10 suppresses tumor angiogenesis and impedes expression of critical angiogenic factors in renal cell carcinoma. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr B18.