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lb611 |
Cell and Molecular Biology, Institute of Cancer Research, London, United Kingdom
ABSTRACT
Cell movement plays a central role in the generation of tumour blood vessels. We are studying how signalling pathways determine movement of endothelial cells. During tube formation studied in an organotypic tissue culture angiogenesis assay, endothelial cells migrate in a 3-dimensional matrix shed by fibroblasts by extending cell protrusions. We have shown that during migration MAPK-ERK opposes Rho-kinase signalling to allow endothelial cell survival and sprouting (1). However, during establishment Rho-kinase activity is up-regulated at cell junctions and is required for the maintenance of vessel quiescence. Inhibition of Rho-kinase switches established tubules to a sprouting phenotype that is Rac dependent. A key determinant of angiogenic sprouting versus establishment is the degree of actomyosin contractility. We show that actomyosin contractility is regulated by Rho family GTPases and VE-cadherin mediated cell-cell adhesion signalling pathways.
REFERENCES
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