MT1-MMP-dependent neovessel formation within the confines of the three-dimensional extracellular matrix
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
During angiogenesis, endothelial cells initiate a tissue-invasive program within an interstitial matrix comprised largely of type I collagen. Extracellular matrix-degradative enzymes, including the matrix metalloproteinases (MMPs) MMP-2 and MMP-9, are thought to play key roles in angiogenesis by binding to docking sites on the cell surface after activation by plasmin- and/or membrane-type (MT) 1-MMP-dependent processes. To identify proteinases critical to neovessel formation, an ex vivo model of angiogenesis has been established wherein tissue explants from gene-targeted mice are embedded within a three-dimensional, type I collagen matrix. Unexpectedly, neither MMP-2, MMP-9, their cognate cell-surface receptors (i.e., beta3 integrin and CD44), nor plasminogen are essential for collagenolytic activity, endothelial cell invasion, or neovessel formation. Instead, the membrane-anchored MMP, MT1-MMP, confers endothelial cells with the ability to express invasive and tubulogenic activity in a collagen-rich milieu, in vitro or in vivo, where it plays an indispensable role in driving neovessel formation.
Originalsprog | Engelsk |
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Tidsskrift | The Journal of Cell Biology |
Vol/bind | 167 |
Udgave nummer | 4 |
Sider (fra-til) | 757-67 |
Antal sider | 11 |
ISSN | 0021-9525 |
DOI | |
Status | Udgivet - 22 nov. 2004 |
ID: 201165293