The investigation of individual anti-angiogenic therapy focused on the control mechanism of matrix remodeling in renal cell carcinoma

本研究的目的是确定肾细胞癌中基质重塑的控制机制，并研究其是否可能成为新的治疗靶点和抗血管生成治疗的敏感标志物。这项研究表明，VHL-非典型PKC-JunB途径不通过HIF（缺氧诱导因子）有助于肾细胞癌的进展，我们实际上证实了来自肾癌细胞系的异种移植物JunB的表达影响肿瘤生长和血管生成。此外，我们确定了基质金属蛋白酶-2（MMP-2）、MMP-9和趋化因子（C-C基序）配体-2（CCL 2）作为JunB的下游效应物。功能分析结果提示，它们有可能成为肾癌血管生成和侵袭的新的分子靶点。

The purpose of this research is to identify a pathway of the control mechanism of matrix remodeling in renal cell carcinoma and to examine whether it could be a new therapeutic target and a sensitive marker of anti-angiogenic therapy. This study indicates that the pathway of VHL-atypical PKC-JunB not through the HIF(hypoxia-inducible factor) contributes to the progression of renal cell carcinoma, and we actually confirmed with xenografts from kidney cancer cell lines that the expression of JunB affected tumor growth and angiogenesis. Moreover, we identified matrix metalloproteinase-2(MMP-2), MMP-9 and chemokine(C-C motif) ligand-2(CCL2) as downstream effectors of JunB. The results of their functional analysis suggest that they have the possibility to be new molecular targets for angiogenesis and invasion of renal cell carcinoma.