[HTML][HTML] Adrenomedullin and calcitonin gene-related peptide receptors in endocrine-related cancers: opportunities and challenges

DL Hay, CS Walker, DR Poyner - Endocrine-related cancer, 2011 - erc.bioscientifica.com
Endocrine-related cancer, 2011erc.bioscientifica.com
Abstract Adrenomedullin (AM), adrenomedullin 2 (AM2/intermedin) and calcitonin gene-
related peptide (CGRP) are members of the calcitonin family of peptides. They can act as
growth or survival factors for a number of tumours, including those that are endocrine-
related. One mechanism through which this occurs is stimulating angiogenesis and
lymphangiogenesis. AM is expressed by numerous tumour types and for some cancers,
plasma AM levels can be correlated with the severity of the disease. In cancer models …
Abstract
Adrenomedullin (AM), adrenomedullin 2 (AM2/intermedin) and calcitonin gene-related peptide (CGRP) are members of the calcitonin family of peptides. They can act as growth or survival factors for a number of tumours, including those that are endocrine-related. One mechanism through which this occurs is stimulating angiogenesis and lymphangiogenesis. AM is expressed by numerous tumour types and for some cancers, plasma AM levels can be correlated with the severity of the disease. In cancer models, lowering AM content or blocking AM receptors can reduce tumour mass. AM receptors are complexes formed between a seven transmembrane protein, calcitonin receptor-like receptor and one of the two accessory proteins, receptor activity-modifying proteins (RAMPs) 2 or 3 to give the AM 1 and AM 2 receptors respectively. AM also has affinity at the CGRP receptor, which uses RAMP1. Unfortunately, due to a lack of selective pharmacological tools or antibodies to distinguish AM and CGRP receptors, the precise receptors and signal transduction pathways used by the peptides are often uncertain. Two other membrane proteins, RDC1 and L1/G10D (the ‘ADMR’), are not currently considered to be genuine CGRP or AM receptors. In order to properly evaluate whether AM or CGRP receptor inhibition has a role in cancer therapy, it is important to identify which receptors mediate the effects of these peptides. To effectively distinguish AM 1 and AM 2 receptors, selective receptor antagonists need to be developed. The development of specific CGRP receptor antagonists suggests that this is now feasible.
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