Comparison of matrix metalloproteinase expression between primary tumors with or without liver metastasis in pancreatic and colorectal carcinomas

Background and Objectives: Matrix metalloproteinases (MMPs) are known to play an important role in carcinoma cell invasion and hematogenous metastasis by mediating the degradation of the extracellular matrix. Methods: We investigated the relationship between MMP-2 and -9 enzymatic activities and liver metastases in human pancreatic and colon carcinomas, using xenograft tumors in nude mice. Results: We found that type IV collagenase activity in pancreatic and colon carcinomas with liver metastases was significantly higher than in pancreatic and colon carcinomas without liver metastases. Gelatin zymography showed the presence of gelatinolytic activity bands at M-r 92,000 and 72,000, indicating MMP-9 and MMP-2, respectively. MMP-2 and -9 expression levels in pancreatic and colon carcinomas with liver metastases were higher than in pancreatic and colon carcinomas without liver metastases. TIMP-2 levels in pancreatic and colon carcinomas with liver metastases were also higher than in those without liver metastases. Conclusions: MMP-2 and MMP-9 expression in primary tumors is associated with liver metastases in pancreatic and colon carcinomas. In addition, the balance of activity between MMP-2, MMP-9, and TIMP-2 may be relevant to carcinoma invasion and metastasis, including, liver metastases in pancreatic and colon carcinoma. (C) 2002Wiley-Liss, Inc.