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Tumor cell invasion through matrigel is regulated by activated matrix metalloproteinase-2.

Authors
  • Deryugina, E I
  • Luo, G X
  • Reisfeld, R A
  • Bourdon, M A
  • Strongin, A
Type
Published Article
Journal
Anticancer research
Publication Date
Jan 01, 1997
Volume
17
Issue
5A
Pages
3201–3210
Identifiers
PMID: 9413149
Source
Medline
License
Unknown

Abstract

We tested the hypothesis that there is a correlation between tumor cell efficiency in activation of matrix metalloproteinase-2 (MMP-2) and invasion through basement membrane-like Matrigel barriers. To generate cells capable of MMP-2 activation, we stably transfected three human tumor cell lines, HT-1080 fibrosarcoma, MCF7 breast carcinoma, and U251.3 glioma with cDNA encoding the full length human membrane-type matrix metalloproteinase-1. Our results show a bimodal correlation between the extent of MMP-2 activation and Matrigel invasion by tumor cells. Cell transfectants characterized by a partial activation of MMP-2 were the most invasive while those with an extensive conversion of MMP-2 proenzyme into enzymatically active forms were the least efficient in invading Matrigel. Modulation of MMP-2 activation by exogenous TIMP-2 reverted the rate of Matrigel invasion by cell transfectants to control levels. We conclude that the regulation of activated MMP-2 in the tumor cells, microenvironment may be critical in facilitating tumor cell invasiveness.

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