BIOMAT Database Logo BIOMAT Database Logo

Integrin alpha2beta1 is the required receptor for endorepellin angiostatic activity. 2008

Benjamin P Woodall, and Alexander Nyström, and Rex A Iozzo, and Johannes A Eble, and Stephan Niland, and Thomas Krieg, and Beate Eckes, and Ambra Pozzi, and Renato V Iozzo
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.

Endorepellin, the C-terminal module of perlecan, has angiostatic activity. Here we provide definitive genetic and biochemical evidence that the functional endorepellin receptor is the alpha2beta1 integrin. Notably, the specific endorepellin binding to the receptor was cation-independent and was mediated by the alpha2 I domain. We show that the anti-angiogenic effects of endorepellin cannot occur in the absence of alpha2beta1. Microvascular endothelial cells from alpha2beta1(-/-) mice, but not those isolated from either wild-type or alpha1beta1(-/-) mice, did not respond to endorepellin. Moreover, syngeneic Lewis lung carcinoma xenografts in alpha2beta1(-/-) mice failed to respond to systemic delivery of endorepellin. In contrast, endorepellin inhibited tumor growth and angiogenesis in the wild-type mice expressing integrin alpha2beta1. We conclude that the angiostatic effects of endorepellin in vivo are mediated by a specific interaction of endorepellin with the alpha2beta1 integrin receptor.

UI MeSH Term Description Entries
D009368 Neoplasm Transplantation Experimental transplantation of neoplasms in laboratory animals for research purposes. Transplantation, Neoplasm,Neoplasm Transplantations,Transplantations, Neoplasm
D009389 Neovascularization, Pathologic A pathologic process consisting of the proliferation of blood vessels in abnormal tissues or in abnormal positions. Angiogenesis, Pathologic,Angiogenesis, Pathological,Neovascularization, Pathological,Pathologic Angiogenesis,Pathologic Neovascularization,Pathological Angiogenesis,Pathological Neovascularization
D010446 Peptide Fragments Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques. Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D004730 Endothelium, Vascular Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components. Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014183 Transplantation, Heterologous Transplantation between animals of different species. Xenotransplantation,Heterograft Transplantation,Heterografting,Heterologous Transplantation,Xenograft Transplantation,Xenografting,Transplantation, Heterograft,Transplantation, Xenograft
D043165 Angiostatic Proteins Proteins that specifically inhibit the growth of new blood vessels (ANGIOGENESIS, PHYSIOLOGIC). Angiostatic Peptides
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines

Related Publications

Benjamin P Woodall, and Alexander Nyström, and Rex A Iozzo, and Johannes A Eble, and Stephan Niland, and Thomas Krieg, and Beate Eckes, and Ambra Pozzi, and Renato V Iozzo
Endorepellin, the C-terminal angiostatic module of perlecan, enhances collagen-platelet responses via the alpha2beta1-integrin receptor.
May 2007, Blood,
Benjamin P Woodall, and Alexander Nyström, and Rex A Iozzo, and Johannes A Eble, and Stephan Niland, and Thomas Krieg, and Beate Eckes, and Ambra Pozzi, and Renato V Iozzo
Proteomic profiling of endorepellin angiostatic activity on human endothelial cells.
February 2008, Proteome science,
Benjamin P Woodall, and Alexander Nyström, and Rex A Iozzo, and Johannes A Eble, and Stephan Niland, and Thomas Krieg, and Beate Eckes, and Ambra Pozzi, and Renato V Iozzo
Integrin alpha2beta1 is a receptor for the cartilage matrix protein chondroadherin.
September 1997, The Journal of cell biology,
Benjamin P Woodall, and Alexander Nyström, and Rex A Iozzo, and Johannes A Eble, and Stephan Niland, and Thomas Krieg, and Beate Eckes, and Ambra Pozzi, and Renato V Iozzo
Endorepellin causes endothelial cell disassembly of actin cytoskeleton and focal adhesions through alpha2beta1 integrin.
July 2004, The Journal of cell biology,
Benjamin P Woodall, and Alexander Nyström, and Rex A Iozzo, and Johannes A Eble, and Stephan Niland, and Thomas Krieg, and Beate Eckes, and Ambra Pozzi, and Renato V Iozzo
Integrin alpha2beta1 is required for regulation of murine wound angiogenesis but is dispensable for reepithelialization.
February 2007, The Journal of investigative dermatology,
Benjamin P Woodall, and Alexander Nyström, and Rex A Iozzo, and Johannes A Eble, and Stephan Niland, and Thomas Krieg, and Beate Eckes, and Ambra Pozzi, and Renato V Iozzo
Role of tyrosine phosphatase SHP-1 in the mechanism of endorepellin angiostatic activity.
November 2009, Blood,
Benjamin P Woodall, and Alexander Nyström, and Rex A Iozzo, and Johannes A Eble, and Stephan Niland, and Thomas Krieg, and Beate Eckes, and Ambra Pozzi, and Renato V Iozzo
Endorepellin, the angiostatic module of perlecan, interacts with both the α2β1 integrin and vascular endothelial growth factor receptor 2 (VEGFR2): a dual receptor antagonism.
July 2011, The Journal of biological chemistry,
Benjamin P Woodall, and Alexander Nyström, and Rex A Iozzo, and Johannes A Eble, and Stephan Niland, and Thomas Krieg, and Beate Eckes, and Ambra Pozzi, and Renato V Iozzo
Enzymatically catalyzed disulfide exchange is required for platelet adhesion to collagen via integrin alpha2beta1.
September 2003, Blood,
Benjamin P Woodall, and Alexander Nyström, and Rex A Iozzo, and Johannes A Eble, and Stephan Niland, and Thomas Krieg, and Beate Eckes, and Ambra Pozzi, and Renato V Iozzo
E-cadherin is a ligand for integrin alpha2beta1.
October 2002, Matrix biology : journal of the International Society for Matrix Biology,
Benjamin P Woodall, and Alexander Nyström, and Rex A Iozzo, and Johannes A Eble, and Stephan Niland, and Thomas Krieg, and Beate Eckes, and Ambra Pozzi, and Renato V Iozzo
The alpha2beta1 integrin: a novel collectin/C1q receptor.
January 2007, Immunobiology,
Copied contents to your clipboard!