Thrombospondin-1 as an endogenous inhibitor of angiogenesis and tumor growth

J Cell Mol Med. Jan-Mar 2002;6(1):1-12. doi: 10.1111/j.1582-4934.2002.tb00307.x.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Amino Acid Sequence
  • Angiogenesis Inhibitors
  • Animals
  • Antineoplastic Agents
  • Cell Division
  • Disease Progression
  • Enzyme Inhibitors / metabolism
  • Models, Biological
  • Molecular Sequence Data
  • Neoplasms / blood supply
  • Neoplasms / pathology*
  • Neovascularization, Pathologic*
  • Neovascularization, Physiologic*
  • Thrombospondin 1 / chemistry
  • Thrombospondin 1 / genetics
  • Thrombospondin 1 / metabolism*
  • Transforming Growth Factor beta / metabolism

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Thrombospondin 1
  • Transforming Growth Factor beta