Growth factor-induced morphological, physiological and molecular characteristics in cerebral endothelial cells

The capacity of vascular endothelial cells to modulate their phenotype in r esponse to changes in environmental conditions is one of the most important characteristics of this cell type. Since different growth factors may play an important signalling role in this adaptive process we have investigated the effect of endothelial cell growth factor (ECGF) on morphological, phys iological and molecular characteristics of cerebral endothelial cells (CECs ), CECs grown in the presence of ECGF and its cofactor heparin exhibit an e pithelial-like morphology (type I CECs), Upon removal of growth factors, CE Cs develop an elongated spindle-like shape (type II CECs) which is accompan ied by the reorganization of actin filaments and the induction of a-actin e xpression. Since one of the most important functions of CECs is the creatio n of a selective diffusion barrier between the blood and the central nervou s system (CNS), we have studied the expression of junction-related proteins in both cell types. We have found that removal of growth factors from endo thelial cultures leads to the downregulation of cadherin and occludin prote in levels. The loss of junctional proteins was accompanied by a significant increase in the migratory activity and an altered protease activity profil e of the cells. TGF-beta 1 suppressed endothelial migration in all experime nts, Our data provide evidence to suggest that particular endothelial funct ions are largely controlled by the presence of growth factors. The differen ces in adhesiveness and migration may play a role in important physiologica l and pathological processes of endothelial cells such as vasculogenesis or tumor progression.