Regulation of nitric oxide signalling by thrombospondin 1: implications for anti-angiogenic therapies

Nat Rev Cancer. 2009 Mar;9(3):182-94. doi: 10.1038/nrc2561. Epub 2009 Feb 5.


In addition to long-term regulation of angiogenesis, angiogenic growth factor signalling through nitric oxide (NO) acutely controls blood flow and haemostasis. Inhibition of this pathway may account for the hypertensive and pro-thrombotic side effects of the vascular endothelial growth factor antagonists that are currently used for cancer treatment. The first identified endogenous angiogenesis inhibitor, thrombospondin 1, also controls tissue perfusion, haemostasis and radiosensitivity by antagonizing NO signalling. We examine the role of these and other emerging activities of thrombospondin 1 in cancer. Clarifying how endogenous and therapeutic angiogenesis inhibitors regulate vascular NO signalling could facilitate development of more selective inhibitors.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • CD36 Antigens / physiology
  • Cyclic GMP / physiology
  • Hemostasis
  • Humans
  • Neoplasms / etiology
  • Nitric Oxide / physiology*
  • Radiation Tolerance
  • Regional Blood Flow
  • Signal Transduction*
  • Thrombospondin 1 / physiology*


  • Angiogenesis Inhibitors
  • CD36 Antigens
  • Thrombospondin 1
  • Nitric Oxide
  • Cyclic GMP