Activity and cellular origin of gelatinases in patients with colon and rectal carcinoma differential activity of matrix metalloproteinase-9

BACKGROUND. Expression and enzymatic activity of gelatinases were examined in biopsy specimens from patients with colon and rectal neoplasms. The obje ctive of this study was to determine whether the activity of these enzymes is altered between tumor areas compared with areas of noninvolved, normal m ucosa and between colon and rectal carcinoma. METHODS. Matrix metalloproteinase (MMP) production was analyzed by Western immunoblot analysis and gelatin zymography. mRNA was determined by quantita tive, real-time polymerase chain reaction analysis. RESULTS. Patients with colon carcinoma (n = 20 patients) showed a significa nt increase in levels of MMP-9 (92 kDa and 88 kDa) and MMP-2 (72 kDa and 62 kDa) in tumor areas compared with noninvolved regions. In contrast, patien ts with rectal carcinoma (n = 10 patients) had revealed the same high activ ity of MMP-9 in tumor regions and corresponding healthy tissue. Confirming activity measurements, in colon tumors, but not in rectal tumors, there was significant up-regulation of MMP-9 transcription compared with healthy tis sue in the same patients. There were no significant changes in the tissue i nhibitor of metalloproteinase-1 protein when colon and rectal tumor tissues were compared with the corresponding noninvolved regions. Cell culture exp eriments revealed fibroblasts as the cellular origin of MMPs. The findings showed that the secretion and activation of gelatinases depend on soluble f actors secreted by tumor cells and are influenced by extracellular matrix c omponents. CONCLUSIONS. This is the first report showing differences in MMP-9 activity between rectal carcinoma and colon carcinoma. Previous results indicating an active involvement of stromal cells in the generation of MMPs during tum or invasion are extended. Because the abundance of gelatinases increases in colorectal carcinoma, inhibitors of these proteases may be of therapeutic value. (C) 2001 American Cancer Society.