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PMID: 11535623 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Proteolytic exposure of a cryptic site within collagen type IV is required for angiogenesis and tumor growth in vivo.

The Journal of cell biology ·Vol. 154 ·No. 5 ·2001-09-03 ·Pages 1069-79

Xu J, Rodriguez D, Petitclerc E, Kim JJ, Hangai M, Moon YS, Davis GE, Brooks PC, Yuen SM

Abstract

Evidence is provided that proteolytic cleavage of collagen type IV results in the exposure of a functionally important cryptic site hidden within its triple helical structure. Exposure of this cryptic site was associated with angiogenic, but not quiescent, blood vessels and was required for angiogenesis in vivo. Exposure of the HUIV26 epitope was associated with a loss of alpha1beta1 integrin binding and the gain of alphavbeta3 binding. A monoclonal antibody (HUIV26) directed to this site disrupts integrin-dependent endothelial cell interactions and potently inhibits angiogenesis and tumor growth. Together, these studies suggest a novel mechanism by which proteolysis contributes to angiogenesis by exposing hidden regulatory elements within matrix-immobilized collagen type IV.

MeSH Terms
Animals Antibodies, Monoclonal/metabolism,pharmacology,therapeutic use Basement Membrane/chemistry,metabolism Binding Sites Cell Adhesion/physiology Cell Movement/physiology Chick Embryo Collagen/chemistry,immunology,metabolism Corneal Neovascularization/chemically induced Diabetic Retinopathy/metabolism,pathology Endothelium, Vascular/metabolism Epitopes/metabolism Humans Matrix Metalloproteinase 2/genetics,metabolism Melanoma/blood supply,pathology Mice Microscopy, Fluorescence Neoplasm Transplantation Neoplasms/drug therapy,metabolism,pathology Neovascularization, Pathologic Neovascularization, Physiologic Peptide Hydrolases/metabolism Protein Binding Protein Denaturation Protein Structure, Tertiary Rats Receptors, Vitronectin/metabolism Retinal Vessels/metabolism Skin/blood supply,metabolism Tumor Cells, Cultured
Chemicals
Antibodies, Monoclonal Epitopes Receptors, Vitronectin Collagen Peptide Hydrolases Matrix Metalloproteinase 2
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Xu J
Department of Radiation Oncology, Kaplan Cancer Center, New York University School of Medicine, New York, NY 10016, USA.
Rodriguez D
Petitclerc E
Kim J J
Hangai M
Moon Y S
Davis G E
Brooks P C
Yuen S M
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200103111
Published
2001-09-03
Pages
1069-79
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2196184
Subset
IM
Grants
NCI NIH HHS · CA086140 · United States
NCI NIH HHS · CA74132 · United States
NHLBI NIH HHS · HL59971 · United States
Corrections
ErratumIn
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External Links
PubMed source DOI: 10.1083/jcb.200103111 PMC Full Text View journal details
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