[Endothelin-1, angiotensin II and cancer]

Med Sci (Paris). 2006 Apr;22(4):416-22. doi: 10.1051/medsci/2006224416.
[Article in French]

Abstract

Endothelin-1 (ET-1) and angiotensin II (AngII), two potent vasoactive peptides involved in the regulation of cardiovascular homeostasis, also induce mitogenic and pro-angiogenic responses in vitro and in vivo. Both peptides are produced by cleavage of inactive precursors by metalloproteases (endothelin-converting enzyme and angiotensin-converting enzyme, respectively) and activate two subtypes of membrane receptors (ETA-R and ETB-R for ET-1, AT1R and AT2R for AngII) that all belong to the superfamily of G-protein coupled receptors. There is increasing evidence that ETA-R, ETB-R and AT1R are expressed in a variety of cancer cells and tissues, and may play a role on tumor growth, angiogenesis and invasion in vivo. This review summarizes the similarities and differences between the ET-1 and AngII systems with regard to their reported effects on various aspects of cancer. In addition to being expressed on vascular endothelium, ET-1 and AngII receptors participate in tumor angiogenesis through the production of the angiogenic factor VEGF. Furthermore, recent clinical studies indicate that a selective ETA-R antagonist has beneficial effects in prostate cancer, suggesting that a similar approach using ETB-R and AT1R blockers might be envisioned. Experimental data presented here suggest that a combined therapy targeting both ET-1 and AngII systems may prove valuable for future treatments of highly angiogenic tumors.

Publication types

  • English Abstract
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use
  • Angiotensin II / drug effects
  • Angiotensin II / physiology*
  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Benzimidazoles / pharmacology
  • Benzimidazoles / therapeutic use
  • Clinical Trials as Topic
  • Endothelin-1 / drug effects
  • Endothelin-1 / physiology*
  • Humans
  • Neoplasm Invasiveness / physiopathology
  • Neoplasms / blood supply
  • Neoplasms / physiopathology*
  • Neovascularization, Pathologic / physiopathology*
  • Receptors, Angiotensin / drug effects
  • Receptors, Angiotensin / physiology
  • Receptors, Endothelin / drug effects
  • Receptors, Endothelin / physiology
  • Tetrazoles / pharmacology
  • Tetrazoles / therapeutic use

Substances

  • Angiogenesis Inhibitors
  • Angiotensin II Type 1 Receptor Blockers
  • Antineoplastic Agents
  • Benzimidazoles
  • Endothelin-1
  • Receptors, Angiotensin
  • Receptors, Endothelin
  • Tetrazoles
  • Angiotensin II
  • candesartan