context dependent role of the cd36 - thrombospondin - histidine-rich glycoprotein axis in tumor angiogenesis and growthcd36的上下文依赖的角色u2014u2014血小板反应蛋白富含组氨酸糖蛋白轴在肿瘤血管生成和增长.pdf

Context Dependent Role of the CD36 - Thrombospondin - Histidine-Rich Glycoprotein Axis in Tumor Angiogenesis and Growth 1,2 2 2 3 2 James Scott Hale , Meizhang Li , Maksim Sinyuk , Willi Jahnen-Dechent , Justin Durla Lathia , Roy Lee Silverstein1,2,4* 1 Department of Biological, Geological and Environmental Sciences, Cleveland State University, Cleveland, Ohio, United States of America, 2 Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation and Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio, United States ¨ of America, 3 Helmholtz Institute for Biomedical Engineering, Rheinisch-Westfalische Technische Hochschule Aachen University Hospital, Aachen, Germany, 4 Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America Abstract The angiogenic switch is a promising therapeutic target in cancer. Work by our laboratory and others has described an important endogenous anti-angiogenic pathway mediated by interactions of CD36, a receptor on microvascular endothelial cells, with proteins containing thrombospondin (TSP) type I repeat domains (TSR). Recent studies revealed that circulating Histidine Rich Glycoprotein (HRG) inhibits the anti-angiogenic potential of the CD36-TSR pathway by functioning as a decoy receptor that binds and sequesters TSR proteins. As tumors of different origin display variable expression profiles of numerous targets, we hypothesized that the TSP-CD36-HRG axis regulates vascularization and growth in the tumor microenvironment in a context, or tumor type, dependent manner. G