Adrenomedullin and calcitonin gene-related peptide receptors in endocrine-related cancers

opportunities and challenges

Debbie L. Hay, Christopher S. Walker, David R Poyner

Research output: Contribution to journalArticle

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 AM1 and AM2 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 AM1 and AM2 receptors, selective receptor antagonists need to be developed. The development of specific CGRP receptor antagonists suggests that this is now feasible.
Original languageEnglish
Pages (from-to)C1-14
Number of pages14
JournalEndocrine-related Cancer
Volume18
Issue number1
Early online date4 Nov 2010
DOIs
Publication statusPublished - 1 Feb 2011

Fingerprint

Endocrine Gland Neoplasms
Calcitonin Gene-Related Peptide Receptors
Adrenomedullin
Adrenomedullin Receptors
Neoplasms
Peptides
Receptor Activity-Modifying Protein 3
Receptor Activity-Modifying Protein 2
Calcitonin Receptor-Like Protein
Lymphangiogenesis
Calcitonin Gene-Related Peptide
Calcitonin
Signal Transduction
Membrane Proteins
Proteins
Pharmacology

Keywords

  • adrenomedullin
  • animals
  • calcitonin gene-related peptide
  • humans
  • neoplasms
  • receptor activity-modifying proteins
  • calcitonin gene-related peptide receptors

Cite this

@article{77cccea3914143a2a4ebb90ecffbfaa1,
title = "Adrenomedullin and calcitonin gene-related peptide receptors in endocrine-related cancers: opportunities and challenges",
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 AM1 and AM2 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 AM1 and AM2 receptors, selective receptor antagonists need to be developed. The development of specific CGRP receptor antagonists suggests that this is now feasible.",
keywords = "adrenomedullin, animals, calcitonin gene-related peptide, humans, neoplasms, receptor activity-modifying proteins, calcitonin gene-related peptide receptors",
author = "Hay, {Debbie L.} and Walker, {Christopher S.} and Poyner, {David R}",
year = "2011",
month = "2",
day = "1",
doi = "10.1677/ERC-10-0244",
language = "English",
volume = "18",
pages = "C1--14",
journal = "Endocrine-related Cancer",
issn = "1351-0088",
publisher = "Society for Endocrinology",
number = "1",

}

Adrenomedullin and calcitonin gene-related peptide receptors in endocrine-related cancers : opportunities and challenges. / Hay, Debbie L.; Walker, Christopher S.; Poyner, David R.

In: Endocrine-related Cancer, Vol. 18, No. 1, 01.02.2011, p. C1-14.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Adrenomedullin and calcitonin gene-related peptide receptors in endocrine-related cancers

T2 - opportunities and challenges

AU - Hay, Debbie L.

AU - Walker, Christopher S.

AU - Poyner, David R

PY - 2011/2/1

Y1 - 2011/2/1

N2 - 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 AM1 and AM2 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 AM1 and AM2 receptors, selective receptor antagonists need to be developed. The development of specific CGRP receptor antagonists suggests that this is now feasible.

AB - 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 AM1 and AM2 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 AM1 and AM2 receptors, selective receptor antagonists need to be developed. The development of specific CGRP receptor antagonists suggests that this is now feasible.

KW - adrenomedullin

KW - animals

KW - calcitonin gene-related peptide

KW - humans

KW - neoplasms

KW - receptor activity-modifying proteins

KW - calcitonin gene-related peptide receptors

UR - http://www.scopus.com/inward/record.url?scp=79251472138&partnerID=8YFLogxK

UR - http://erc.endocrinology-journals.org/content/18/1/C1

U2 - 10.1677/ERC-10-0244

DO - 10.1677/ERC-10-0244

M3 - Article

VL - 18

SP - C1-14

JO - Endocrine-related Cancer

JF - Endocrine-related Cancer

SN - 1351-0088

IS - 1

ER -