Identification of amino acids essential for the antiangiogenic activity of tumstatin and its use in combination antitumor activity.

ABSTRACT: Tumstatin is an angiogenesis inhibitor that binds to alphavbeta3 integrin and suppresses tumor growth. Previous deletion mutagenesis studies identified a 25-aa fragment of tumstatin (tumstatin peptide) with in vitro antiangiogenic activity. Here, we demonstrate that systemic administration of this tumstatin peptide inhibits tumor growth and angiogenesis. Site-directed mutagenesis identified amino acids L, V, and D as essential for the antiangiogenic activity of tumstatin. The tumstatin peptide binds to alphavbeta3 integrin on proliferating endothelial cells and localizes to select tumor endothelium in vivo. Using 3D molecular modeling, we identify a putative interaction interface for tumstatin peptide on alphavbeta3 integrin. The antitumor activity of the tumstatin peptide, in combination

SUBMITTER: Eikesdal HP 

PROVIDER: S-EPMC2567489 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature