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

Int J Cancer. 1999 Oct 22;84(5):470-7. doi: 10.1002/(sici)1097-0215(19991022)84:5<470::aid-ijc4>3.0.co;2-d.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Endometrial Neoplasms / enzymology*
  • Enzyme Activation
  • Female
  • Humans
  • Immunoblotting
  • Immunoenzyme Techniques
  • Lymphatic Metastasis
  • Matrix Metalloproteinase 7
  • Metalloendopeptidases / analysis
  • Metalloendopeptidases / biosynthesis*
  • Metalloendopeptidases / genetics
  • Middle Aged
  • RNA, Messenger / analysis
  • Tissue Inhibitor of Metalloproteinase-1 / analysis
  • Tissue Inhibitor of Metalloproteinase-2 / analysis


  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-2
  • Metalloendopeptidases
  • Matrix Metalloproteinase 7