Adrenomedullin and cancer

Adrenomedullin (AM) is a pluripotent hormone with structural similarities to calcitonin gene-related peptide (CGRP), which is expressed by many tissues in the body and shows a remarkable range of effects mediated by paracrine/autocrine and possibly endocrine mechanisms. AM has been implicated as a m...

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Bibliographic Details
Published in:Regulatory peptides 2003-04, Vol.112 (1), p.175-183
Main Authors: Zudaire, E, Martı́nez, A, Cuttitta, F
Format: Article
Language:English
Subjects:
Adrenomedullin
Angiogenesis Inducing Agents - metabolism
Animals
Apoptosis
Cell Hypoxia
Humans
Immunologic Surveillance
Neoplasms - etiology
Neoplasms - immunology
Neoplasms - metabolism
Peptides - physiology
Rats
Receptors, Adrenomedullin
Receptors, Peptide - metabolism
Signal Transduction
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Summary:Adrenomedullin (AM) is a pluripotent hormone with structural similarities to calcitonin gene-related peptide (CGRP), which is expressed by many tissues in the body and shows a remarkable range of effects mediated by paracrine/autocrine and possibly endocrine mechanisms. AM has been implicated as a mediator of several pathologies such as cardiovascular and renal disorders, sepsis, inflammation, diabetes and cancer, among others. AM is expressed in a variety of tumors where it aggravates several of the molecular and physiological features of malignant cells. AM has been shown to be a mitogenic factor stimulating growth in several cancer types and to encourage a more aggressive tumor phenotype. In addition, AM is an apoptosis survival factor for cancer cells and an indirect suppressor of the immune response through its binding protein, complement factor H, and regulation in expression of cytokines. AM plays an important role in environments subjected to low oxygen tensions, which is a typical feature in the proximity of solid tumors. Under these conditions, AM is upregulated through a hypoxia-inducible factor 1 (HIF-1)-dependent pathway and acts as a potent angiogenic factor promoting neovascularization. The collective findings brought together over the last years place AM as a major regulator of carcinogenesis-tumor progression and identifies its autocrine loop as a putative target for developing new strategies against human cancers.
ISSN:0167-0115
1873-1686
DOI:10.1016/S0167-0115(03)00037-5