Adrenomedullin as a therapeutic target in angiogenesis.
BACKGROUND
Hypoxia, a frequent characteristic in the microenvironment of solid tumors, leads to adrenomedullin (AM) upregulation through the hypoxia inducible factor-1 pathway, explaining its high expression in a variety of malignant tissues. AM is believed to play an important role in tumor progression and angiogenesis in many cancers. Therefore, it could become a new therapeutic target.


METHODS
We performed a review of the literature based on published data to highlight AM's critical roles in tumor cell growth and cancer invasiveness, and its involvement in tumor angiogenesis through promotion of recruitment of hematopoietic progenitors, vascular morphogenesis, and blood vessel stabilization and maturation. Inhibition of AM has antitumoral effects linked to antiangiogenic effects but in some cases also to direct antiproliferative activity on cancer cells. Several studies demonstrated that systemic inhibition of AM receptors was well tolerated in murine models.


RESULTS
The goal of this review is to inform readers about the role of AM in tumor angiogenesis and cancer progression and, therefore, about its possible place as a new therapeutic target.


CONCLUSIONS
Taken together, these data support targeting the AM pathway as a new potential therapy in cancer, complementary to other existing treatments.
Deville
Jean-Laurent
JL
Inserm UMR 911-CRO2, Faculté de Médecine Timone, 13385 Marseille Cedex 05, F-13000, France. jean-laurent.DEVILLE@ap-hm.fr
Salas
Sébastien
S
Figarella-Branger
Dominique
D
Ouafik
L'Houcine
L
Daniel
Laurent
L
D053607:Adrenomedullin / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D018450:Disease Progression; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D051379:Mice; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D051793:Hypoxia-Inducible Factor 1; D042461:Vascular Endothelial Growth Factor A; D053607:Adrenomedullin