CD146 is a co-receptor for VEGFR-2 in tumor angiogenesis. Blood. 2012 Jun 20.

Blood, 2012 Jun 20.doi: 10.1182/blood-2012-01-406108

CD146 is a co-receptor for VEGFR-2 in tumor angiogenesis.

Jiang T, Zhuang J, Duan H, Luo Y, Zeng Q, Fan K, Yan H, Lu D, Ye Z, Hao J, Feng J, Yang D, Yan X.

Key Laboratory of Protein & Peptide Pharmaceutical, National Laboratory of Biomacromolecules, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology & Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

Abstract

CD146 is a novel endothelial biomarker and plays an essential role in angiogenesis. However, its role in the molecular mechanism underlying angiogenesis still remains poorly understood. Here, we show that CD146 directly interacts with VEGFR-2 on endothelial cells as well as at the molecular level. The detail structural basis of CD146 binding to VEGFR-2 is identified. In addition, we show that CD146 is required in VEGF-induced VEGFR-2 phosphorylation, AKT/p38 MAPKs/NF-κB activation and thus promotion of endothelial cell migration as well as microvascular formation. Furthermore, anti-CD146 AA98 or CD146 siRNA abrogated all VEGFR-2 activation induced by VEGF. An in vivo angiogenesis assay showed that VEGF-promoted microvascular formation was impaired in the endothelial conditional knockout of CD146 (CD146(EC-KO)). Importantly, our animal experiments demonstrated that anti-CD146 (AA98) and anti-VEGF (Bevacizumab) play an additive inhibitory effect on xenografted human pancreatic and melanoma tumor. Our findings suggest that CD146 is a new co-receptor for VEGFR-2 and a promising target for blocking tumor-related angiogenesis.

相关报道：http://www.ibp.cas.cn/kyjz/zxdt/201207/t20120721_3619652.html

全文链接：http://bloodjournal.hematologylibrary.org/content/early/2012/06/20/blood-2012-01-406108.long

或 http://dx.doi.org/10.1182/blood-2012-01-406108