New functions for non-collagenous domains of human collagen type IV. Novel integrin ligands inhibiting angiogenesis and tumor growth in vivo.

Petitclerc E, Boutaud A, Prestayko A, Xu J, Sado Y, Ninomiya Y, Sarras MP, Hudson BG, Brooks PC
J Biol Chem. 2000 275 (11): 8051-61

PMID: 10713126 · DOI:10.1074/jbc.275.11.8051

Collagen type IV is a major component of the basal lamina of blood vessels. Six genetically distinct collagen type IV chains have been identified and are distributed in a tissue-specific manner. Here we define a novel function for soluble non-collagenous (NC1) domains of the alpha2(IV), alpha3(IV), and alpha6(IV) chains of human collagen type IV in the regulation of angiogenesis and tumor growth. These NC1 domains were shown to regulate endothelial cell adhesion and migration by distinct alpha(v) and beta(1) integrin-dependent mechanisms. Systemic administration of recombinant alpha2(IV), alpha3(IV), and alpha6(IV) NC1 domains potently inhibit angiogenesis and tumor growth, whereas alpha1(IV), alpha4(IV), and alpha5(IV) showed little if any effect. These findings suggest that specific NC1 domains of collagen type IV may represent an important new class of angiogenesis inhibitors.

MeSH Terms (23)

Amino Acid Sequence Angiogenesis Inhibitors Animals Antigens, CD Basement Membrane Carcinoma Cell Adhesion Chick Embryo Collagen Endothelium, Vascular Extraembryonic Membranes Humans Integrin alphaV Integrin beta1 Integrins Ligands Melanoma Models, Molecular Molecular Sequence Data Neovascularization, Pathologic Peptide Fragments Protein Structure, Tertiary Urinary Bladder Neoplasms

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