Adrenomedullin production is increased in colorectal adenocarcinomas; its relation to matrix metalloproteinase-9.

Abstract:

:Adrenomedullin (AM) is highly expressed in various cancer cell lines, suggesting a possible association with cancer growth. In the present study, we examined the expression and/or concentration of AM, its related peptide, adrenomedullin2/intermedin (AM2/IMD) and their receptors in human colorectal cancer and the surrounding normal tissue. In addition, we assessed the correlation between the expression of AM and AM2/IMD with that of vascular endothelial growth factor (VEGF)-A and matrix metalloproteinase (MMP)-9. Using a specific immunoradiometric assay, we found that AM concentrations were 2-11-fold higher in colorectal cancer tissues than in the surrounding normal tissues. Moreover, real-time quantitative RT-PCR showed that the expression levels of preproAM (+548%), preproAM2/IMD (+2674%), calcitonin receptor-like receptor (CLR) (+518%), receptor activity modifying protein (RAMP)2 (+281%), RAMP3 (+178%), VEGF-A (+277%) and MMP-9 (+864%) mRNAs were significantly higher in cancer tissues than in the surrounding normal tissues, and there was a positive correlation between the gene expressions of MMP-9 and preproAM (r=0.352; p=0.005), but not with preproAM2/IMD (r=0.041, p=0.406). Both AM and AM2/IMD immunoreactivity were detected mainly within cancer cells, whereas MMP-9 immunoreactivity was mostly seen in the surrounding stroma. These findings suggest that AM produced in colorectal tumors acts in concert with MMP-9 in the stroma to contribute to the pathogenesis of colorectal cancer.

journal_name

Peptides

journal_title

Peptides

authors

Hikosaka T,Tsuruda T,Nagata S,Kuwasako K,Tsuchiya K,Hoshiko S,Inatsu H,Chijiiwa K,Kitamura K

doi

10.1016/j.peptides.2011.07.012

subject

Has Abstract

pub_date

2011-09-01 00:00:00

pages

1825-31

issue

9

eissn

0196-9781

issn

1873-5169

pii

S0196-9781(11)00287-7

journal_volume

32

pub_type

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