Identification of an active site on the laminin α4 chain globular domain that binds to αvβ3 integrin and promotes angiogenesis

Angiogenesis is important for wound healing, tumor growth, and metastasis. The laminin α4 chain, a component of laminin-8 and -9, is expressed in endothelial cell basement membranes. It mediates endothelial cell adhesion by binding with its receptors such as αvβ3 integrin and participates in new blood vessel formation. In this study, we found the recombinant laminin α4LG modules (rLG1-3, rLG1, and rLG2) mediate HUVECs adhesion. The attachment of HUVECs to the rLG2 was specifically inhibited by a function-blocking monoclonal antibody LM609 specific for αvβ3 integrin. Using deletion mutants of the α4LG2 revealed the HUVECs-adhesion site is located in amino acids 1121–1139. A synthetic G1121–1139 peptide could be attached by HUVECs at same efficiency with the rLG2 and promoted angiogenesis in CAM. In conclusion, we have identified a new αvβ3 integrin-interacting peptide within laminin α4 G domain. This suggests that G1121–1139 peptide-containing proteins may perform their biological functions by interacting with αvβ3 integrin.