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 and metastasis. Matrix metalloproteinase-2 degrades type IV collagen and laminin, major components of the basement membrane. Membrane type 1 matrix metalloproteinase activates the latent form of matrix metalloproteinase-2. We studied changes in membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 expression in relation to the tumor differentiation of hepatocellular carcinomas. Activity of matrix metalloproteinase-2 was also evaluated in hepatocellular carcinomas and noncancerous tissues. Overall, 37 hepatocellular carcinomas were studied. Expression of membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 was determined by either immunohistochemistry (n=37) or in situ hybridization (n=6). Changes in membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 expression were evaluated in relation to tumor differentiation. Gelatinolytic activities were analyzed by gelatin zymography (n=4). Membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 were detected in hepatoma cells and stromal cells. In addition, these matrix metalloproteinases were detected in the same hepatoma cells. Increased expression of membrane type 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 noncancerous tissues. These findings indicate that increased expression of membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 was associated with tumor dedifferentiation, suggesting that these matrix metalloproteinases are intimately involved in the invasion of hepatocellular carcinomas.
Ogata
R
R
Second Department of Medicine, Kurume University School of Medicine, Japan.
Torimura
T
T
Kin
M
M
Ueno
T
T
Tateishi
Y
Y
Kuromatsu
R
R
Shimauchi
Y
Y
Sakamoto
M
M
Tamaki
S
S
Sata
M
M
Tanikawa
K
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000473:pathology / Q000648:ultrastructure; D002454:Cell Differentiation; D017364:Collagenases / Q000096:biosynthesis*; D005260:Female; D018093:Gelatinases / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008113:Liver Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D020781:Matrix Metalloproteinase 1; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000096:biosynthesis*; D008854:Microscopy, Electron; D008875:Middle Aged
D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1