[Endothelin-1, angiotensin II and cancer].
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.
Cazaubon
Sylvie
S
Institut Cochin, Département de Biologie Cellulaire, 22, rue Méchain, 75014 Paris, France. cazaubon@cochin.inserm.fr
Deshayes
Frédérique
F
Couraud
Pierre-Olivier
PO
Nahmias
Clara
C
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000804:Angiotensin II / Q000187:drug effects / Q000502:physiology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use; D001713:Biphenyl Compounds; D002986:Clinical Trials as Topic; D019332:Endothelin-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D009369:Neoplasms / Q000098:blood supply / Q000503:physiopathology*; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000502:physiology; D017466:Receptors, Endothelin / Q000187:drug effects / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use
D020533:Angiogenesis Inhibitors; D047228:Angiotensin II Type 1 Receptor Blockers; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D019332:Endothelin-1; D011945:Receptors, Angiotensin; D017466:Receptors, Endothelin; D013777:Tetrazoles; D000804:Angiotensin II; C081643:candesartan