MATRIX-METALLOPROTEASE-2 (MMP-2) AND MATRIX-METALLOPROTEASE-9 (MMP-9)TYPE-IV COLLAGENASES IN COLORECTAL-CANCER

Using quantitative zymography, we measured activity of the type IV col lagenases metalloprotease 2 (MMP-2) and MMP-9 in 192 biopsies from col orectal carcinomas, adenomas, and normal bowel. The median level of MM P-9 in samples from Dukes' stage A (n = 18) or C (n = 48) tumors was s ignificantly higher than in stage B carcinomas (n = 65), adenomas (n = 25), and normals (n = 36; P = 0.0001). The median level of active MMP -2 was significantly higher in stage A or C compared with adenomas (P = 0.0001) and normals (P = 0.0001). The median level of inactive MMP-2 was higher in all Dukes' stages compared with normals and adenomas (P = 0.0001). There was a significant increase in inactive MMP-2 from Ja ss prognostic groups I-IV (P = 0.006) but no correlation with the acti ve enzyme. MMP activity was not related to tumor differentiation, colo n versus rectal location, or disease-free, 5-year survival. All groups expressed mRNA for both enzymes, but there were quantitative and loca tional differences in MMP-2 mRNA expression between normal, benign, an d malignant tissues. Thus MMP-2 is controlled at the level of mRNA and protein production and activation in colorectal cancer, and active MM P-2 and MMP-9 enzymes are associated strongly with Dukes' A and C stag es of the disease. Variations in MMP levels with the stage or prognost ic group of colorectal cancer reflect their differing stromal content.