Recombinant semaphorin 6A-1 ectodomain inhibits in vivo growth factor and tumor cell line-induced angiogenesis.

摘要: The Semaphorins are a large family of transmembrane, GPI-anchored and secreted proteins that play an important role in neuronal endothelial cell guidance. A human gene related to the class 6 Semaphorin family, 6A-1 (Sema 6A-1) was identified by homology-based genomic mining. Recent implication Sema 3 members tumor angiogenesis our expression analysis suggested might effect neovascularization. mRNA elevated several renal tissue samples relative adjacent nontumor from same patient. transcript also expressed majority clear carcinoma (RCC) lines lesser extent cells. To test angiogenesis, we engineered, purified soluble extracellular domain (Sema-ECD). Sema-ECD screened variety cell-based assays both vitro vivo. In vitro, blocked VEGF-mediated migration. These effects were explained part observation cells inhibited Src, FAK ERK phosphorylation. vivo, mouse Matrigel demonstrated intraperitoneal administration recombinant bFGF/VEGF line-induced findings reveal novel therapeutic utility for (Sema-ECD) as inhibitor growth factor well tumor-induced angiogenesis.