Introduction: MMP-2, 7 and 9 are enzymes that degrade and remodel the extracellular matrix, while COX-2 is an inducible enzyme involved in prostaglandin synthesis. Overexpression of these enzymes is associated with progression of of colorectal adenomas to carcinoma, however there are no data documenting co-expression of these markers with correlation to pathologic stage in human colorectal carcinoma.
Methods: Thirty-four patients underwent colectomy, snap freezing of normal mucosa and primary colorectal carcinoma. AJCC stage at the time of resection was: II(n=14); III(n=10); IV(n=10). Taqman quantitative RT-PCR was used to measure gene expression and normalized to beta-actin RNA expression. Data presented as mean±SEM, analyzed by the Wilcoxon Signed Ranks test, Significance defined as p<0.05.
Results: The mean age was 62±4 years, with 20 males and 14 females. COX-2, MMP-2, MMP-7 and MMP-9 were all significantly overexpressed in colorectal carcinoma compared to normal mucosa. COX-2 was the only marker analyzed that was significantly correlated with increasing pathologic stage. The major increase was seen in Stage IV patients.
Conclusion: COX-2, MMP-2, MMP-7 and MMP-9 are significantly overexpressed in human colorectal carcinomas suggesting all are involved with the development of a malignant phenotype, however, none except COX-2 increases with an increase in pathologic stage. Investigation of the biologic activity of selective COX-2 inhibitors on prostaglandin synthesis and effects on MMP gene expression is warranted for potential therapeutic interventions.
COX-2 and MMPs in Colorectal Cancer
copy#/ng b-actin RNA normal mucosa carcinoma
COX-2 246 ± 50 908 ± 160
MMP-2 3150 ± 400 7599 ± 1200
MMP-7 50 ± 30 2400 ± 920
MMP-9 198 ± 63 348 ± 50