Tumor cell invasion through matrigel is regulated by activated matrix metalloproteinase-2.
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.
Deryugina
E I
EI
La Jolla Institute for Experimental Medicine, CA 92037, USA.
Luo
G X
GX
Reisfeld
R A
RA
Bourdon
M A
MA
Strongin
A
A
D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D004338:Drug Combinations; D004789:Enzyme Activation; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D007797:Laminin; D020781:Matrix Metalloproteinase 1; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011509:Proteoglycans; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D004338:Drug Combinations; D016023:Integrins; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D019716:Tissue Inhibitor of Metalloproteinase-2; D003094:Collagen; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1