Research article summary (published 13 Nov 2009):

Expression and role of adrenomedullin in renal tumors and value of its mRNA levels as prognostic factor in clear-cell renal carcinoma.

Full Abstract

Antiangiogenic therapies are used for advanced clear-cell renal carcinomas (cRCC), but without curative possibilities, underlining the need for new therapeutic targets. Adrenomedullin (AM), a multifunctional peptide, is highly expressed in several tumors and plays an important role in angiogenesis and tumor growth through its receptors: calcitonin receptor-like receptor/receptor activity-modifying protein 2 and 3 (CLR/RAMP2 and CLR/RAMP3). In this study, real-time quantitative reverse-transcription-PCR showed AM mRNA levels were higher in cRCC and in chromophobe renal carcinomas (chRCC) than in normal renal tissue. Interestingly, AM mRNA expression in cRCC correlated strongly with VEGF-A mRNA expression. Immunohistochemically, AM, CLR and RAMP2 were localized in the carcinomatous epithelial compartment of cRCC. Interestingly, RAMP3 immunostaining was found only in the inflammatory cells that infiltrated tumors, suggesting a cross talk between tumor cells and the microenvironment. We also observed that cRCC cells BIZ and 786-O expressed and secreted AM into the culture medium. In vitro, exogenous AM treatment stimulated cell proliferation, migration and invasion, indicating the cell can respond to AM. The action of AM was specific and was mediated by the CLR/RAMP2 and CLR/RAMP3 receptors. Clinical data showed the prognostic value of AM. High AM mRNA levels were associated with an increased risk of relapse after curative nephrectomy for cRCC. These findings highlight the implication of the AM pathway in the metastatic process and the prognostic relevance of AM in cRCC and point to a potential new therapeutic target.

Author information

Author/s: Deville, Jean-Laurent (JL); Bartoli, Catherine (C); Berenguer, Caroline (C); Fernandez-Sauze, Samantha (S); Kaafarani, Itidal (I); Delfino, Christine (C); Fina, Frederic (F); Salas, Sébastien (S); Muracciole, Xavier (X); Mancini, Julien (J); Lechevallier, Eric (E); Martin, Pierre-Marie (PM); Figarella-Branger, Dominique (D); Ouafik, L'Houcine (L); Daniel, Laurent (L);

Affiliation: Inserm, UMR 911-CRO2, Marseille, France. jldeville(-atsign-)infonie.fr

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't

Journal: International journal of cancer. Journal international du cancer (Int J Cancer), published in United States. (Language: eng)

Reference: 2009-Nov; vol 125 (issue 10) : pp 2307-15

Dates: Created 2009/09/28; Completed 2009/11/05;

PMID: 19610056, status: MEDLINE (last retrieval date: 11/5/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adrenomedullin - genetics Adult Aged Aged, 80 and over Blotting, Western Carcinoma, Renal Cell - genetics; secondary Cell Adhesion Cell Movement Cell Proliferation Female Gene Expression Regulation - physiology Humans Immunoenzyme Techniques Intracellular Signaling Peptides and Proteins - genetics; metabolism Kidney - metabolism; pathology

Kidney - metabolism; pathology Kidney Neoplasms - genetics; pathology Male Membrane Proteins - genetics; metabolism Middle Aged Neoplasm Invasiveness Neoplasm Recurrence, Local - genetics; metabolism; pathology Prognosis RNA, Messenger - genetics; metabolism Receptors, Calcitonin - genetics; metabolism Reverse Transcriptase Polymerase Chain Reaction Survival Rate Tumor Cells, Cultured Vascular Endothelial Growth Factor A - genetics; metabolism Young Adult

Associated Chemicals: CLR protein, human (0) ; Intracellular Signaling Peptides and Proteins (0) ; Membrane Proteins (0) ; RNA, Messenger (0) ; Receptors, Calcitonin (0) ; VEGFA protein, human (0) ; Vascular Endothelial Growth Factor A (0) ; calcitonin receptor-like receptor (0) ; receptor-activity-modifying protein (0) ; Adrenomedullin (148498-78-6)

Related articles

These are the highest related articles currently in the database:

• Expression and effect of adrenomedullin in pheochromocytoma. 30 Jul 2006
• Adrenomedullin peptide: gene expression of adrenomedullin, its receptors and receptor activity modifying proteins, and receptor binding in rat testis--actions on testosterone secretion. May 2006
• Pharmacological and kinetic characterization of adrenomedullin 1 and calcitonin gene-related peptide 1 receptor reporter cell lines. 2008
• Adrenomedullin and CGRP interact with endogenous calcitonin-receptor-like receptor in endothelial cells and induce its desensitisation by different mechanisms. 27 Feb 2006
• Adrenomedullin is induced by hypoxia and enhances pancreatic cancer cell invasion. 29 Jun 2007
• Adrenomedullin increases the expression of calcitonin-like receptor and receptor activity modifying protein 2 mRNA in human microvascular endothelial cells. 30 Jul 2006
• Increased interferon alpha receptor 2 mRNA levels is associated with renal cell carcinoma metastasis. 13 Aug 2007
• Adrenomedullin enhances invasion by trophoblast cell lines. 23 May 2005
• [Alterations of intermedin and its receptor system in oleic acid-induced acute lung injury of rats] 16 Oct 2006
• Expression of adrenomedullin and its receptors in the human adrenal cortex and aldosteronomas. 29 Sep 2001

See 100+ related articles.

Related Article Map

Legend: - FREE Full text Article. - Abstract only. - Title only. More help.

See a large map of 100+ related articles.