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Endothelial cell lumen and vascular guidance tunnel formation requires MT1-MMP–dependent proteolysis in 3-dimensional collagen matrices
- Publication Year :
- 2009
- Publisher :
- American Society of Hematology, 2009.
-
Abstract
- Here we show that endothelial cells (EC) require matrix type 1-metalloproteinase (MT1-MMP) for the formation of lumens and tube networks in 3-dimensional (3D) collagen matrices. A fundamental consequence of EC lumen formation is the generation of vascular guidance tunnels within collagen matrices through an MT1-MMP-dependent proteolytic process. Vascular guidance tunnels represent a conduit for EC motility within these spaces (a newly remodeled 2D matrix surface) to both assemble and remodel tube structures. Interestingly, it appears that twice as many tunnel spaces are created than are occupied by tube networks after several days of culture. After tunnel formation, these spaces represent a 2D migratory surface within 3D collagen matrices allowing for EC migration in an MMP-independent fashion. Blockade of EC lumenogenesis using inhibitors that interfere with the process (eg, integrin, MMP, PKC, Src) completely abrogates the formation of vascular guidance tunnels. Thus, the MT1-MMP-dependent proteolytic process that creates tunnel spaces is directly and functionally coupled to the signaling mechanisms required for EC lumen and tube network formation. In summary, a fundamental and previously unrecognized purpose of EC tube morphogenesis is to create networks of matrix conduits that are necessary for EC migration and tube remodeling events critical to blood vessel assembly.
- Subjects :
- Immunology
Integrin
Plenary Paper
Motility
Matrix metalloproteinase
Biology
Biochemistry
Substrate Specificity
medicine
Matrix Metalloproteinase 14
Humans
RNA, Small Interfering
Cells, Cultured
Endothelial Cells
Cell Biology
Hematology
Anatomy
Cell biology
Endothelial stem cell
medicine.anatomical_structure
Tube morphogenesis
biology.protein
Biocatalysis
Blood Vessels
Collagen
Lumen (unit)
Proto-oncogene tyrosine-protein kinase Src
Blood vessel
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....9e0db161b189a844a59ac0aec9b0b2d2