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Differential Expression of Matrix Metalloproteinase (MMP)-2, MMP-9, and Membrane Type 1-MMP in Hepatocellular and Pancreatic Adenocarcinoma: Implications for Tumor Progression and Clinical Prognosis
In the present study, we used in situ hybridization to study 36 primary hepatocellular carcinomas (HCCs) and 35 pancreatic adenocarcinomas to analyze the expressions of membrane-type 1 matrix metalloproteinase (MT1-MMP), MMP-2, and MMP-9 mRNAs. In HCCs, MT1-MMP mRNA was mainly expressed by cancer ce...
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Published in: | Clinical cancer research 2000-07, Vol.6 (7), p.2726-2734 |
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Main Authors: | , , , |
Format: | Article |
Language: | English |
Subjects: | |
Online Access: | Get full text |
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Summary: | In
the present study, we used in situ hybridization to
study 36 primary hepatocellular carcinomas (HCCs) and 35 pancreatic
adenocarcinomas to analyze the expressions of membrane-type 1 matrix
metalloproteinase (MT1-MMP), MMP-2, and MMP-9 mRNAs. In HCCs, MT1-MMP
mRNA was mainly expressed by cancer cells and to a lesser extent by
stromal cells. MMP-2 mRNA was expressed predominantly by cells of tumor
stroma, whereas MMP-9 mRNA was seen mainly in neoplastic epithelial
cells. In pancreatic adenocarcinomas, MT1-MMP and MMP-9 mRNA were seen
at moderate levels both in cancer and in stromal cells, whereas MMP-2
mRNA was predominantly expressed by the tumor stroma. Antigens of
MMP-2, MMP-9, and MT1-MMP immunolocalized to the neoplastic epithelium
and to the stromal cells in both tumor types. In gelatin zymography,
increased amounts of latent and active MMP-2 were found in tumor
samples of HCC as compared with adjacent nontumorous liver tissue. On
the other hand, the latent form of MMP-9 was found in almost equal
amounts both in tumor and normal liver samples, but its active form was
present only in HCC.
Expression of MT1-MMP mRNA had a tendency to be associated with a lower
degree of differentiation in HCC, but such association was not noticed
in pancreatic tumors. Correlation to the clinical data showed that
MT1-MMP expression had a strong statistical association with a poor
outcome of patients ( P < 0.01). A similar tendency
was also observed in pancreatic adenocarcinomas, but the association
did not reach statistical significance. MMP-2 and MMP-9 mRNA expression
did not have significant correlation with prognosis. The results of
this study support the previous suggestions of the importance of
MT1-MMP for malignant growth and indicate that increased MT1-MMP mRNA
expression by tumor cells in HCCs and pancreatic adenocarcinomas may
have prognostic significance. |
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ISSN: | 1078-0432 1557-3265 |