Korean J Intern Med.  2000 Dec;15(3):171-178.

Expression of Tissue Inhibitors of Metalloproteinases (TIMPs) in Hepatocellular Carcinoma

• Joo YE
• Seo YH
• Lee WS
• Kim HS
• Choi SK
• Rew JS
• Park CS
• Kim SJ

Abstract

BACKGROUND: Matrix metalloproteinases (MMPs) have been implicated in the remodelling of extracellular matrix (ECM), including basement membrane. ECM remodelling is associated with pathological processes, including hepatic fibrosis, tumor invasion and metastasis. Tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 were known to inhibit MMP-9 and MMP-2, respectively. In the present study, we examined the expression of TIMP-1 and TIMP-2 in surgical specimen pairs of hepatocellular carcinoma and nontumoral liver and the correlation between their expression and clinicopathological characteristics.
METHODS
The localization of both transcripts and protein of TIMP-1 and TIMP-2 was studied by using in situ hybridization and immunohistochemistry.
RESULTS
TIMP-1 and TIMP-2 mRNA transcripts were found in tumor cells, hepatocyte, sinusoidal cells, endothelial cells and stromal cells. Signal intensity of TIMP-1 was stronger than that of TIMP-2. The results of immunohistochemical stainings were concordant with those obtained by in situ hybridization. Expression of TIMP-1 and TIMP-2 was observed in tumorous tissue, in nontumorous tissue and in the portions of the tumors adjacent to the capsules. However, a clear difference in TIMP-1 and TIMP-2 mRNA expression was not observed among the three tissue types. The intensity of TIMP-2 expression was generally weaker than that of TIMP-1, and the intensity of TIMP-1 and TIMP-2 mRNA expression did not correlate with variable clinicopathological characteristics.
CONCLUSION
TIMPs was expressed in tumor cells and many cell types of the nontumoral liver. Further investigations for TIMPs' unknown functional role are needed.

Keyword

Tissue inhibitor of metalloproteinases; Carcinoma, Hepatocellular; Insitu hybridization; Immunohistochemistry

MeSH Terms

Adult
Aged
Carcinoma, Hepatocellular/pathology
Carcinoma, Hepatocellular/metabolism*
Female
Human
Immunohistochemistry
Liver Neoplasms/pathology
Liver Neoplasms/metabolism*
Male
Middle Age
RNA, Messenger/analysis
Tissue Inhibitor-of Metalloproteinase-2/physiology
Tissue Inhibitor-of Metalloproteinase-2/genetics*
Tissue Inhibitor-of Metalloproteinase-2/analysis
Tissue-Inhibitor of Metalloproteinase-1/physiology
Tissue-Inhibitor of Metalloproteinase-1/genetics*
Tissue-Inhibitor of Metalloproteinase-1/analysis