Analysis of MT1-MMP and MMP2 expression in human gastric cancers.
Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a presumed activator of MMP2, which is one of the major proteinases in tumor cell invasion. In this study, we determined the clinico-pathologic significance of MT1-MMP expression in 68 human gastric carcinomas. The tumor-normal ratio (T/N ratio) of MTI-MMP expression was determined by reverse transcription-polymerase chain reaction analysis. To visualize the localization of MT1-MMP, an immunohistochemical study was performed. In addition, a gelatin zymography was done to examine the activation ratio of MMP2, and a correlation between MT1-MMP expression and activation of MMP2 was studied. The expression of MT1-MMP mRNA was higher in tumor tissue than in corresponding normal tissue in most cases. The mean value of the T/N ratio was 4.8. Twenty cases with T/N > or = 4.8 showed significantly deeper invasion and higher frequency of lymph node metastasis than 48 cases with T/N < 4.8. MT1-MMP expression was an independent factor influencing both tumor invasion of the gastric wall and lymph node metastasis. Although MT1-MMP expression was not an independent prognostic factor, the patients with T/N > or = 4.8 showed a significantly worse prognosis than those with T/N < 4.8. An immunohistochemical study demonstrated that MT1-MMP expression was mainly recognized in the tumor cells. There was a significant correlation between MT1-MMP expression and activation of MMP2. Our findings suggest that: 1) the expression of MT1-MMP may influence prognosis via tumor invasion of the gastric wall and lymph node metastasis, and 2) MT1-MMP activation of MMP2 may be clinically relevant in gastric carcinoma tumors.
Mori
M
M
Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan.
Mimori
K
K
Shiraishi
T
T
Fujie
T
T
Baba
K
K
Kusumoto
H
H
Haraguchi
M
M
Ueo
H
H
Akiyoshi
T
T
D000368:Aged; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000378:metabolism*; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D018093:Gelatinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2