Differential expression of type I collagen and cellular fibronectin isoforms in endothelial cell variants

Endothelial cells in vivo and in vitro are inherently capable of manifesting more than one phenotype. Most endothelial cells in culture, even when maintained at confluent density for an extended period, exhibit only the typical polygonal morphology. Other cultures, albeit few, are characterized by rapid formation of variant "sprout" cells once the cobblestone monolayer is established. In vivo studies have revealed sprout cell formation to be one of the early events in neovascularization. Therefore, elucidation of the factors involved in this process is needed to gain an understanding of the sprouting phenomena. To this end, two morphologically distinct bovine endothelial cell clones derived from a fetal left ventricle were characterized. One culture of cells stably displayed the conventional polygonal phenotype, in contrast to the second culture in which an interconnecting network of sprout cells reproducibly developed beneath the cobblestone monolayer. Analysis of extracellular matrix proteins and RNA transcripts revealed that the sprouting clone showed induction of type I collagen and a shift in fibronectin RNA processing resulting in synthesis of the cellular isoforms. These collagenous and non-collagenous matrix molecules may serve in some manner to affect the processes required during angiogenesis, that is, cell division, cell migration and cell shape change.