DIFFERENTIAL EXPRESSION OF OSTEOPONTIN, PC4, AND CEC5, A NOVEL MESSENGER-RNA SPECIES, DURING IN-VITRO ANGIOGENESIS

The formation of new capillaries from preexisting blood vessels, a pro cess termed angiogenesis, plays a key role in many physiological and p athological conditions such as wound healing, embryogenesis, and tumor growth, The aim of this study was to identify changes in endothelial cell gene expression specifically associated with angiogenesis. Using an in vitro model and the differential display strategy, we compared g ene expression patterns of rat microvascular endothelial cells culture d in two (2D) and three-dimensional (3D) culture, In 2D culture, the c ells express actin and proliferate, whereas in 3D culture actin expres sion is downregulated, and the cells are mitotically quiescent and reo rganize into vascular tubes. We identified three differentially expres sed genes, osteopontin, PC4, and CEC5, a novel mRNA species, with homo logy to calmodulin-dependent protein kinases. The expression patterns were confirmed by Northern blot analysis, In conclusion, the analysis of gene expression in endothelial cells in 2D and 3D culture allows th e identification of genes differentially expressed during angiogenesis . These genes or proteins may serve as targets for therapeutic modulat ion of angiogenesis. (C) 1998 Academic Press.