Background: Matrilysin is a metalloproteinase (MMP-7) abundantly produced by malignant epithelial cells and has been associated with invasion and metastasis. The tissue level and activity state of matrilysin was evaluated in 66 pre-malignant adenomas and in normal mucosa and tumors from 174 patients with colorectal carcinomas in relation with their genotype (two MMP-7 SNPs).
Patients and Methodology: Matrilysin protein levels and SNPs were determined by respectively a specific activity assay detecting total and active matrilysin and PCR-based techniques. The co-expression of matrilysin and neo-angiogenesis marker CD105 was examined by immunohistochemistry and ELISA.
Findings: Total matrilysin levels increased gradually in the normal tissue-adenoma-carcinoma sequence correlating with the grade of the adenomas and stage of the cancers. Matrilysin activity however was only enhanced in adenomas with severe dysplasia and malignant carcinomas. MMP-7 SNP-153C>T correlated especially with active matrilysin in cancer tissue. Matrilysin activity and MMP-7 SNP-153C>T showed independent significant correlation with overall survival of the patients. Immunohistochemistry showed matrilysin mainly in malignant cells especially at the invasive front and in CD105 positive endothelial cells. CD105 levels correlated particularly with active matrilysin.
Conclusion: Matrilysin up-regulation is associated with dysplasia in adenomas and therefore an early event in colorectal carcinogenesis. However, only enhanced matrilysin activity has independent prognostic value for colorectal cancer patient survival. MMP7 SNP-153C>T does not correlate with enhanced tumor matrilysin levels, but does with matrilysin activity. The increased levels of matrilysin might in part be derived from neo-angiogenic endothelial cells.