Abstract
Adrenomedullin (AM) is a regulatory peptide whose involvement in tumour progression is becoming more relevant with recent studies. AM is produced and secreted by the tumour cells but also by numerous stromal cells including macrophages, mast cells, endothelial cells, and vascular smooth muscle cells. Most cancer patients present high levels of circulating AM and in some cases these higher levels correlate with a worst prognosis. In some cases it has been shown that the high AM levels return to normal following surgical removal of the tumour, thus indicating the tumour as the source of this excessive production of AM. Expression of this peptide is a good investment for the tumour cell since AM acts as an autocrine/paracrine growth factor, prevents apoptosis-mediated cell death, increases tumour cell motility and metastasis, induces angiogenesis, and blocks immunosurveillance by inhibiting the immune system. In addition, AM expression gets rapidly activated by hypoxia through a HIF-1α mediated mechanism, thus characterizing AM as a major survival factor for tumour cells. Accordingly, a number of studies have shown that inhibition of this peptide or its receptors results in a significant reduction in tumour progression. In conclusion, AM is a great target for drug development and new drugs interfering with this system are being developed.
Highlights
Adrenomedullin (AM) is a regulatory peptide that was first isolated in 1993 from human pheochromocytoma extracts by Kitamura et al [1]
It belongs to the amylin/calcitonin gene-related peptide (CGRP) super-family, which includes CGRP, amylin and intermedin, named adrenomedullin 2 [5,6,7]
RAMP3-null mice appear normal until old age (9-10 months), at which point they have less weight than their wild-type littermates [47]. These results provide support to the hypothesis that RAMP2 and RAMP3 have distinct physiological functions in embryogenesis, adulthood, and old age
Summary
Adrenomedullin (AM) is a regulatory peptide that was first isolated in 1993 from human pheochromocytoma extracts by Kitamura et al [1]. Similar results were obtained when xenografting human glioblastoma cells, who express high basal levels of AM Both density of blood vessels and cell growth were decreased when an antibody against AM was administered intratumourally [128]. Adrenomedullin and cancer treatment Several strategies have been proposed to inhibit AMinduced tumour growth, including AM mRNA rybozyme which modulates AM expression, and other approaches targeting AM binding to its receptor for example anti-AM blocking antibodies, small nonpeptide molecules, receptor antagonists, truncated peptides, e.g. AM22–52 (AMA) and PAMP12-20 [167,192]. We must be careful with the interpretation of previous data until clinical trials have been performed
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