CD146 is a coreceptor for VEGFR-2 in tumor angiogenesis

被引：217

作者：

Jiang, Tianxia ^{[1
]}

Zhuang, Jie ^{[1
]}

Duan, Hongxia ^{[1
]}

Luo, Yongting ^{[1
]}

Zeng, Qiqun ^{[1
]}

Fan, Kelong ^{[1
]}

Yan, Huiwen ^{[1
]}

Lu, Di ^{[1
]}

Ye, Zhongde ^{[1
]}

Hao, Junfeng ^{[1
]}

Feng, Jing ^{[1
]}

Yang, Dongling ^{[1
]}

Yan, Xiyun ^{[1
]}

机构：

[1] Chinese Acad Sci, Inst Biophys, Chinese Acad Sci Univ Tokyo Joint Lab Struct Viro, Natl Lab Biomacromol,Key Lab Prot & Peptide Pharm, Beijing 100101, Peoples R China

来源：

BLOOD | 2012年 / 120卷 / 11期

基金：

中国国家自然科学基金;

关键词：

ENDOTHELIAL GROWTH-FACTOR; CELL-ADHESION MOLECULE; PHASE-III TRIAL; ANTI-CD146; MONOCLONAL-ANTIBODY; INHIBITS ANGIOGENESIS; BREAST-CANCER; BEVACIZUMAB; MIGRATION; CD44; EXPRESSION;

D O I：

10.1182/blood-2012-01-406108

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

CD146 is a novel endothelial biomarker and plays an essential role in angiogenesis; however, its role in the molecular mechanism underlying angiogenesis remains poorly understood. In the present study, we show that CD146 interacts directly with VEGFR-2 on endothelial cells and at the molecular level and identify the structural basis of CD146 binding to VEGFR-2. In addition, we show that CD146 is required in VEGF-induced VEGFR-2 phosphorylation, AKT/p38 MAPKs/NF-kappa B activation, and thus promotion of endothelial cell migration and microvascular formation. Furthermore, we show that anti-CD146 AA98 or CD146 siRNA abrogates 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)). Our animal experiments demonstrated that anti-CD146 (AA98) and anti-VEGF (bevacizumab) have an additive inhibitory effect on xenografted human pancreatic and melanoma tumors. The results of the present study suggest that CD146 is a new coreceptor for VEGFR-2 and is therefore a promising target for blocking tumor-related angiogenesis. (Blood. 2012;120(11):2330-2339)

引用

页码：2330 / 2339

页数：10

共 48 条

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Involvement of gicerin, a cell adhesion molecule, in the portal metastasis of rat colorectal adenocarcinoma cells [J].