Enhanced production and activation of matrix metalloproteinase-7 (matrilysin) in human endometrial carcinomas.
We examined production and tissue localization of 7 different matrix metalloproteinases (MMP-1, -2, -3, -7, -8, -9 and -13) and 2 tissue inhibitors of metalloproteinases (TIMP-1 and -2) in human endometrial-carcinoma tissues. Sandwich enzyme immunoassays showed enhanced production of MMP-7, MMP-8 and MMP-9 as well as TIMP-1 in the carcinoma tissues compared with non-carcinoma endometrial tissues. Among these MMPs, only the amount of MMP-7 correlated with clinicopathological factors of the carcinomas. The level was significantly 6.8-fold higher in the patient group with lymph-node metastases than in that without metastases (p < 0.05), and also increased with the progress of the clinical stage. MMP-7 was immunolocalized predominantly to the carcinoma cells in 73% of the cases, while MMP-8 and MMP-9 were immunostained in the inflammatory cells infiltrated in the carcinoma tissues. Immunoblotting revealed a definite band for the zymogen of MMP-7 (proMMP-7) of 28 kDa in 82% of the carcinoma samples, while only a faint band for proMMP-7 was seen in 57% of the non-carcinoma endometrial samples. Active MMP-7 species of 19 kDa and its activity were demonstrated in the carcinoma samples with proMMP-7 production by immunoblotting and zymography, respectively. RT-PCR using a specific primer pair for MMP-7 demonstrated expression in 86% of the carcinoma tissue and in 57% of the control tissue samples. In situ hybridization showed carcinoma cells selectively expressing MMP-7 mRNA. These data suggest that, among the 7 MMPs examined, MMP-7 may play a key role in invasion and lymph-node metastasis of human endometrial carcinomas.
Ueno
H
H
Department of Molecular Immunology and Pathology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
Yamashita
K
K
Azumano
I
I
Inoue
M
M
Okada
Y
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016889:Endometrial Neoplasms / Q000201:enzymology*; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D020783:Matrix Metalloproteinase 7; D008666:Metalloendopeptidases / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis
D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D008666:Metalloendopeptidases; D020783:Matrix Metalloproteinase 7