Tumor progression: the effects of thrombospondin-1 and -2

Int J Biochem Cell Biol. 2004 Jun;36(6):1038-45. doi: 10.1016/j.biocel.2004.01.008.


The thrombospondins (TSPs) are a family of proteins that regulate tissue genesis and remodeling. In many tumors, down-regulation of TSPs accompanies activation of oncogenes or inactivation of tumor suppresser genes and appears to be a prerequisite for the aquisition of a pro-angiogenic phenotype. The normal suppression of angiogenesis by TSP-1 and -2 involves multiple mechanisms including direct interaction with vascular endothelial cell growth factor (VEGF), inhibition of matrix metalloproteinase 9 (MMP9) activation, inhibition of endothelial cell migration and induction of endothelial cell apoptosis. The importance of down-regulation of TSPs for tumor progression is further established by the fact that several different approaches that are designed to increase the levels of TSP-1 or -2 in tumor tissue inhibit tumor growth. These approaches include cell-based gene therapy, low dose chemotherapeutics and systemic delivery of recombinant proteins or synthetic peptides that include type 1 repeat (TSR) sequences. Initial studies indicate that these reagents, in combination with established approaches for the treatment of cancer, will offer more efficacious therapies.

Publication types

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

MeSH terms

  • Down-Regulation
  • Humans
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / therapy*
  • Neovascularization, Pathologic / therapy
  • Signal Transduction
  • Thrombospondin 1 / genetics
  • Thrombospondin 1 / metabolism*
  • Thrombospondin 1 / therapeutic use
  • Thrombospondins / genetics
  • Thrombospondins / metabolism*
  • Thrombospondins / therapeutic use


  • Thrombospondin 1
  • Thrombospondins
  • thrombospondin 2