Enhanced expression of tissue inhibitors of metalloproteinases in human colorectal tumors.

Matrix metalloproteinases (MMP), such as 72 kDa type IV collagenase (MMP-2) and 92 kDa type IV collagenase (MMP-9), play an important role in tumor invasion and metastasis. Tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) are specific inhibitors of MMP. To evaluate the expression of TIMP-1, TIMP-2, MMP-2, and MMP-9 in human colorectal cancer, surgical specimens of primary colorectal cancer (66 cases) and liver metastases (10 cases) were examined by Northern and dot-blot hybridization. The levels of TIMP-1, MMP-2 and MMP-9 mRNA were significantly higher in primary colorectal cancers than in their adjacent normal tissues, and those of the mRNAs for all four genes were significantly higher in liver metastases than in normal colorectal tissues. Higher levels of TIMP-1 mRNA were positively correlated with lymph node metastasis and the five-year survival, and higher levels of TIMP-1 and TIMP-2 mRNA were positively correlated with the Dukes classification. Our findings suggest that the expression of TIMP-1 and TIMP-2 is closely correlated with the progression of human colorectal cancer.