Matrix metalloproteinase 2 and 9 activity in patients with colorectal cancer liver metastasis.

Abstract

Matrix metalloproteinases (MMPs) have been reported to play an important role in tumour cell invasion and metastasis. The bioactivity of MMPs in liver metastasis from colorectal cancer was investigated and correlated with clinicopathological variables. Thirty-two patients underwent resection of colorectal cancer liver metastases. Latent and active forms of MMP were measured in tissue extracts, by means of quantitative gelatin zymography and a fluorometric activity assay. Broad-spectrum MMP activity, and levels of both active and latent forms of MMP-2 and MMP-9, were higher in tissues containing metastatic tumour than in normal liver tissue. Median metastatic to normal tissue ratios were 15.0 and 17.6 for active and proMMP-2 respectively, and those for active and proMMP-9 were 6.2 and 2.9. The ratios of active to latent enzyme were higher in metastatic tissue than in normal tissue. Lowered MMP-2 activity was associated with large metastatic lesions and increased proMMP-9 levels with preoperative chemotherapy. Both MMP-2 and MMP-9 activity were linked unfavourably to early recurrent disease. These data suggest a role for MMPs in colorectal cancer liver metastasis, but indicate different roles for individual MMPs.