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Simultaneous determination of matrix metalloproteinase (MMP)-7, MMP-1, -3, and -13 gene expression by multiplex PCR in colorectal carcinomas.

Roeb E, Arndt M, Jansen B, Schumpelick V, Matern S

Medical Clinic III, Rheinisch-Westfälische Technische Hochschule Aachen, Pauwelsstrasse 30, 52057 Aachen, Germany. eroeb@ukaachen.de.

BACKGROUND AND AIMS: MMP-7, a member of the matrix metalloproteinase family, is believed to play a significant role in the growth and proliferation of colon cancer cells. The aim of this study was to evaluate MMP-7 gene expression in comparison with MMP-1, MMP-3, and MMP-13 in patients with resectable rectal and colon cancer by a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). MATERIALS AND METHODS: Biopsy samples of tumor ( n=30) and distant normal mucosa ( n=30) from 30 patients were obtained intraoperation. Messenger (m)RNA was extracted from all of the tissue samples and reverse transcribed to double-stranded cDNA. Semi-quantitative RT-PCR was performed to study the MMP gene expression in both the tumor and normal mucosal specimens. MMP mRNA values were expressed relative to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) for each sample. RESULTS: In all 30 cases an increase in MMP-7 mRNA expression was detected in the cancerous tissue ( p=0.00004). In 21 out of 30 cases an increase in MMP-13 mRNA ( p=0.023) and in 22 out of 30 cases an increase in MMP-3 mRNA ( p=0.075) was detected in the cancerous tissue. In contrast, there was no significant change in the MMP-1 expression of normal and cancerous mucosal specimens in either colon or rectal carcinomas. There were no significant differences between rectum and colon carcinomas. CONCLUSION: Taking into account our earlier studies, we conclude that most cases of colorectal carcinogenesis are characterized by enhanced expression of MMP-7, -13, -3 and the gelatinases, whereas MMP-1-expression is very inconsistent and not overexpressed in many cases. MMP-7 inhibition as well as inhibition of MMP-13 and MMP-3 may be a useful preventive or therapeutic adjunct in colorectal cancer.

Published 13 October 2004 in Int J Colorectal Dis, 19(6): 518-24.
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