Forskning ved Københavns Universitet - Københavns Universitet


MT1-MMP-dependent neovessel formation within the confines of the three-dimensional extracellular matrix

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Tae-Hwa Chun
  • Farideh Sabeh
  • Ichiro Ota
  • Hedwig Murphy
  • Kevin T McDonagh
  • Holmbeck, Kenn
  • Henning Birkedal-Hansen
  • Edward D Allen
  • Stephen J Weiss

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.

TidsskriftThe Journal of Cell Biology
Udgave nummer4
Sider (fra-til)757-67
Antal sider11
StatusUdgivet - 22 nov. 2004

ID: 201165293