| First Author | Jiang T | Year | 2012 |
| Journal | Blood | Volume | 120 |
| Issue | 11 | Pages | 2330-9 |
| PubMed ID | 22718841 | Mgi Jnum | J:189203 |
| Mgi Id | MGI:5444601 | Doi | 10.1182/blood-2012-01-406108 |
| Citation | Jiang T, et al. (2012) CD146 is a coreceptor for VEGFR-2 in tumor angiogenesis. Blood 120(11):2330-9 |
| abstractText | 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-kappaB 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. |
