Type IV collagen alpha6 chain-derived noncollagenous domain 1 (alpha6(IV)NC1) inhibits angiogenesis and tumor growth.
Type IV collagen is a major component of vascular basement membranes. The noncollagenous (NC1) domains of several alpha-chains of type IV collagen reveal a capacity to inhibit angiogenesis and tumor growth. Here, we demonstrate that the NC1 domain of the alpha6 chain of type IV collagen (alpha6NC1) is an endogenous inhibitor of angiogenesis and tumor growth. Recombinant alpha6NC1 inhibits human endothelial cell proliferation and neovascularization of Matrigel plugs in mice. The alpha6NC1 suppresses the growth of subcutaneously transplanted Lewis lung carcinoma and also spontaneous pancreatic insulinomas that develop in the Rip1Tag2 mice. Inhibition of tumor growth is associated with significantly diminished microvascular density. Collectively, our results demonstrate that alpha6NC1 is an endogenous inhibitor of angiogenesis and tumor growth.
Mundel
Thomas M
TM
Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
Yliniemi
Anna-Maija
AM
Maeshima
Yohei
Y
Sugimoto
Hikaru
H
Kieran
Mark
M
Kalluri
Raghu
R
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001672:Biocompatible Materials; D015153:Blotting, Western; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000188:drug therapy*; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen; D024141:Collagen Type IV; D004338:Drug Combinations; D004591:Electrophoresis, Polyacrylamide Gel; D042783:Endothelial Cells / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D007340:Insulinoma / Q000098:blood supply / Q000188:drug therapy*; D007797:Laminin; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008833:Microcirculation / Q000187:drug effects; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D011509:Proteoglycans; D011994:Recombinant Proteins / Q000494:pharmacology
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D024141:Collagen Type IV; D004338:Drug Combinations; D007797:Laminin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011509:Proteoglycans; D011994:Recombinant Proteins; C059485:matrigel; D003094:Collagen