Matrix metalloproteinases, their tissue inhibitors and colorectal cancer staging

Background: Matrix metalloproteinases (MMPs) and their tissue inhibitors (T IMPs) are important in tumour invasion and metastasis. The levels of MMPs, TIMPs and total MMP activity were compared in paired colorectal tumour (n = 50) and normal tissue (n = 49) samples and correlated with clinical and pa thological staging. Methods: Gelatin zymography (MMP-2 and MMP-9), enzyme-linked immunosorbent assays (MMP-1, MMP-3, TIMP-1 and TIMP-2) and quenched fluorescent substrate hydrolysis (total MMP activity) were employed in resection specimens from 50 patients, four with adenomas and 46 with colorectal cancer. Results: The levels of active MMP-2 and MMP-9 and total MMP-1, MMP-3 and TI MP-1 were significantly greater in tumour tissue than in normal colon (e.g. TIMP-1 tumour median 72 (range 25-351) versus normal 26 (4-107) ng per mg total protein content; P < 0.05); however, TIMP-2 levels were significantly greater in normal tissue (P < 0.05). Total MMP activity was significantly greater in tumour than in normal tissue (15 025 (1750-174 400) versus 7250 (750-354 650) pmol l(-1) min(-1) mg protein(-1) ; P < 0.05). Correlations w ere found between both MMP and TIMP levels and pathological tumour staging. MMP-1 appeared to be most important as its concentration correlated positi vely with Dukes staging, tumour differentiation and lymphatic invasion. Conclusion: The levels of the studied MMPs and total MMP activity were upre gulated in colorectal tumours. MMP-1 is important in colorectal cancer prog ression.