Signaling Mechanisms of Endogenous Angiogenesis Inhibitors Derived from Type IV Collagen

• Published in: Gene Regulation and Systems Biology Vol. 2007; no. 1; pp. 217 - 226
• Main Authors: Sudhakar, Akulapalli, Boosani, Chandra S.
• Format: Journal Article Book Review
• Language: English
• Published: London, England SAGE Publishing 01-01-2007; SAGE Publications; Sage Publications Ltd; Libertas Academica
• Subjects: Angiogenesis; angiogenesis inhibitors; Basement membranes; Cancer; Collagen (type IV); Differentiation; endostatin; Gene regulation; Growth factors; Proteolysis; Review; Reviews; Tumors; VEGF, vascular endothelial cell growth factor; SCC-PSA1, teratocarcinoma cell line; ECM, extra cellular matrix; bFGF, basic fibroblast growth factor; VBM, vascular basement membrane; α1–α6(IV)NC1, non-collagenous a1–a6 chains of Type IV collagen domains; MMP, matrix metalloproteinase; MLEC, mouse lung endothelial cells; HUVEC, human umbilical vein endothelial cell
• ISSN: 1177-6250; 1177-6250
• DOI: 10.4137/GRSB.S345

Akulapalli Sudhakar1,2,3 and Chandra S. Boosani1 1Cell Signaling and Tumor Angiogenesis Laboratory, Department of Genetics, Boys Town National Research Hospital, Omaha, NE 68132. 2Department of Biomedical Sciences, Creighton University, School of Medicine, Omaha, NE, 68178. 3Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198.Abstract: Vascular basement membrane (VBM) derived molecules are regulators of certain biological activities such as cell growth, differentiation and angiogenesis. Angiogenesis is regulated by a systematic controlled balance between VBM derived antiangiogenic factors and proangiogenic growth factors. In the normal physiological state, equilibrium is maintained between the antiangiogenic and proangiogenic factors. The antiangiogenic factors (molecules), which are generated by the proteolytic cleavage of the VBM, include; α1 chain non-collagenous (NC1) domain of type XVIII collagen (endostatin) and the NC1 domains from the alpha chains of Type IV collagen considered as endogenous angiogenesis inhibitors. These collagen derived NC1 domains have a pivotal role in the regulation of tumor angiogenesis, thus making them attractive alternate candidates for cancer therapies. In this review we illustrate a comprehensive overview of the knowledge gained from the signaling mechanisms of Type IV collagen derived endogenous inhibitors in angiogenesis.