Increased expression of membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 with tumor dedifferentiation in hepatocellular carcinomas

Destruction of the extracellular matrices is required for tumor invasion an d metastasis. Matrix metalloproteinase-2 degrades type IV collagen and lami nin, major components of the basement membrane. Membrane type 1 matrix meta lloproteinase activates the latent form of matrix metalloproteinase-2. We s tudied changes in membrane type 1 matrix metalloproteinase and matrix metal loproteinase-2 expression in relation to the tumor differentiation of hepat ocellular carcinomas. Activity of matrix metalloproteinase-2 was also evalu ated in hepatocellular carcinomas and noncancerous tissues. Overall, 37 hep atocellular carcinomas were studied. Expression of membrane type 1 matrix m etalloproteinase and matrix metalloproteinase-2 was determined by either im munohistochemistry (n = 37) or in situ hybridization (n = 6). Changes in me mbrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 expre ssion were evaluated in relation to tumor differentiation. Gelatinolytic ac tivities were analyzed by gelatin zymography (n = 4). Membrane type 1 matri x metalloproteinase and matrix metalloproteinase-2 were detected in hepatom a cells and stromal cells. In addition, these matrix metalloaro-teinases we re detected in the same hepatoma cells. Increased expression of membrane ty pe 1 matrix metalloproteinase and matrix metalloproteinase-2 was associated with tumor dedifferentiation. The active form of matrix metalloproteinase- 2 was more strongly expressed by hepatocellular carcinomas than by noncance rous tissues. These findings indicate that increased expression of membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 was associa ted with tumor dedifferentiation, suggesting that these matrix metalloprote inases are intimately involved in the invasion of hepatocellular carcinomas . Copyright (C) 1999 by W.B. Saunders Company.