Enhanced production and activation of matrix metalloproteinase-7 (matrilysin) in human endometrial carcinomas

Hirohisa Ueno, Kaname Yamashita, Isao Azumano, Masaki Inoue, Yasunori Okada

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78 Citations (Scopus)


We examined production and tissue localization of 7 different matrix metalloproteinases (MMP-I, -2, -3, -7, -8, -9 and -13) and 2 tissue inhibitors of metalloproteinases (Tl MP-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-I 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 métastases than in that without métastases (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.

Original languageEnglish
Pages (from-to)470-477
Number of pages8
JournalInternational Journal of Cancer
Issue number5
Publication statusPublished - 1999
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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