Thrombospondin-1 as an endogenous inhibitor of angiogenesis and tumor growth.
Thrombospondin-1 (TSP-1) is a matricellular glycoprotein that influences cellular phenotype and the structure of the extracellular matrix. These effects are important components of the tissue remodeling that is associated with angiogenesis and neoplasia. The genetic mutations in oncogenes and tumor suppressor genes that occur within tumor cells are frequently associated with decreased expression of TSP-1. However, the TSP-1 that is produced by stromal fibroblasts, endothelial cells and immune cells suppresses tumor progression. TSP-1 inhibits angiogenesis through direct effects on endothelial cell migration and survival and through indirect effects on growth factor mobilization. TSP-1 that is present in the tumor microenvironment also acts to suppress tumor cell growth through activation of transforming growth factor beta in those tumor cells that are responsive to TGF beta. In this review, the molecular basis for the role of TSP-1 in the inhibition of tumor growth and angiogenesis is summarized.
Lawler
Jack
J
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA. jlawler@caregroup.harvard.edu
D000595:Amino Acid Sequence; D020533:Angiogenesis Inhibitors; D000818:Animals; D000970:Antineoplastic Agents; D002455:Cell Division; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000098:blood supply / Q000473:pathology*; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic; D019700:Thrombospondin 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D019700:Thrombospondin 1; D016212:Transforming Growth Factor beta