title: Relation of enhanced secretion of active matrix metalloproteinases with tumor spread in human hepatocellular carcinoma.
abstract: OBJECTIVE
  Matrix metalloproteinases have been implicated in invasion and metastasis of various human malignant tumors, but its role in human hepatocellular carcinoma has not been characterized in detail. The aim of the present study was to examine the secretion and activation of metalloproteinases in liver tissues from patients with hepatocellular carcinoma and evaluate its relationship with clinicopathologic characteristics.
  
  
  METHODS
  Activity of metalloproteinases was measured in 30 surgical specimen pairs of human primary hepatocellular carcinoma and adjacent nontumoral liver and in five cultured human hepatoma cell lines using zymography. A comparison of this activity with clinicopathological features was made.
  
  
  RESULTS
  In the liver tissues, enhanced secretion of active forms of gelatinase A and matrilysin was associated with portal venous invasion (P < 0.05, respectively), intrahepatic metastasis (P < 0.05, respectively), and recurrence within the first postoperative year (P < 0.01 and P < 0.05, respectively). Enhanced messenger RNA expression for membrane type 1-matrix metalloproteinase was observed in 22 of 30 cases and associated with capsule invasion and the activation of progelatinase A (P < 0.05, respectively).
  
  
  CONCLUSIONS
  Active gelatinase A, active matrilysin, and membrane type 1-matrix metalloproteinase may play an important role in tumor spread of human hepatocellular carcinoma.
authors.affiliation: First Department of Internal Medicine, Sapporo Medical University, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yamamoto
authors.forename: F
authors.initials: F
authors.lastname: Itoh
authors.forename: Y
authors.initials: Y
authors.lastname: Adachi
authors.forename: H
authors.initials: H
authors.lastname: Sakamoto
authors.forename: M
authors.initials: M
authors.lastname: Adachi
authors.forename: Y
authors.initials: Y
authors.lastname: Hinoda
authors.forename: K
authors.initials: K
authors.lastname: Imai
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D005109:Extracellular Matrix / Q000201:enzymology*; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D008666:Metalloendopeptidases