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| Three-dimensional type I collagen lattices induce coordinate expression of matrix metalloproteinases MT1-MMP and MMP-2 in microvascular endothelial cells |
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| Author(s): Haas TL, Davis SJ, Madri JA |
| Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 273 Issue: 6 Pages: 3604-3610 Published: FEB 6 1998 |
| Times Cited: 226 References: 47 |
| Abstract: Matrix metalloproteinases (MMPs) are hypothesized to play a key role in the processes of endothelial cell migration and matrix remodeling during angiogenesis. We utilized an in vitro model of microvascular endothelial cell angiogenesis, cells cultured within a collagen matrix, to investigate the MMP profile of endothelial cells undergoing angiogenesis. We demonstrated by gelatin zymography that monolayer cultures (two-dimensional) of endothelial cells constitutively expressed low levels of latent MMP-2, but that culture in a three-dimensional collagen matrix increased the total amount of MMP-2 mRNA and protein, Furthermore, 51% of total MMP-2 protein was activated in the three-dimensional culture lysates, compared with 3.5% in two-dimensional culture, The mRNA and protein of MT1-MMP, the putative activator of MMP-2, were up-regulated in endothelial cells cultured in three-dimensional as compared with two dimensional culture, Treatment of cultures with MMP inhibitors blocked activation of MMP-2 and inhibited formation of endothelial cell networks within the collagen gel, Induction of MT1-MMP and MMP-2 appeared to be specific to collagen, inasmuch as culture of the endothelial cells on top of, or within, a Matrigel(R) matrix neither increased total MMP-2 nor increased activation of MMP-2. These results suggest that MT1-MMP activation of MMP-2 occurs in endothelial cells undergoing angiogenesis, that this activation has a functional role in endothelial cell organization, and that specific matrix interactions may be critical for the increased expression of MT1-MMP and MMP-2. |
| Document Type: Article |
| Language: English |
| Reprint Address: Madri, JA (reprint author), Yale Univ, Sch Med, Dept Pathol, LH115,310 Cedar St, New Haven, CT 06510 USA |
Addresses:
1. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA |
| Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: YV427 |
| ISSN: 0021-9258 |
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