Overcoming the resistance to molecular-targeted therapy for renalcell carcinoma by analyzing of VHL control mechanism in a HIF independent manner

我们之前报道过pvhl -非典型PKC-JunB通路以缺氧诱导因子（HIF）独立的方式促进透明细胞肾细胞癌（ccRCC）的进展，并检测到趋化因子（C-C基序）配体-2 （CCL2）是其下游效应之一。为了获得克服现有抗vegf疗法耐药的发现，本研究的目的是研究CCL2作为ccRCC新治疗靶点的效用。在本研究中，我们评估了CCL2在ccRCC临床标本中的表达，证实了CCL2的表达参与了ccRCC细胞系异种移植物的肿瘤生长和血管形成。此外，我们证实了CCL2中和抗体对来自ccRCC临床标本和细胞系的异种移植物的抗肿瘤作用。这些结果提示CCL2可能是ccRCC的潜在治疗靶点。

We previously reported that the pathway of pVHL-atypical PKC-JunB in a hypoxia-inducible factor (HIF) independent manner contributed to the progression in clear cell renal cell carcinoma (ccRCC), and detected chemokine (C-C motif) ligand-2 (CCL2) as one of a downstream effector of it. To obtain findings of overcoming resistance to existing anti-VEGF therapies, the purpose of this research is to investigate the utility of CCL2 as a novel therapeutic target in ccRCC. In this study, we evaluated CCL2 expression in ccRCC clinical specimens, and confirmed that CCL2 expression involved in tumor growthand vascularization in xenograft derived from ccRCC cell lines. Moreover, we confirmed the anti-tumor effect of CCL2 neutralization antibodies to xenograft derived from ccRCC clinical specimens and cell lines. These results suggest that CCL2 could be a potential therapeutic target in ccRCC.