Gp38k, a protein synthesized by vascular smooth muscle cells, stimulates directional migration of human umbilical vein endothelial cells

Gp38k is a 383-amino-acid secreted glycoprotein expressed by cultured vascu lar smooth muscle cells during the time of transition from a proliferating monolayer culture to a nonproliferating multilayered (differentiated) cultu re. Expression continues as the cell culture forms multicellular nodules, B ecause this transition period involves active cell migration, we evaluated the effects of exogenously added gp38k on vascular endothelial cell (HUVEC) migration and chemotaxis, Here we demonstrate that gp38k acts as a chemoat tractant for HUVECs and stimulates cell migration in Boyden chambers at a l evel comparable to that achieved with the known endothelial cell chemoattra ctant bFGF. The migration effect is neutralized by the presence of a polycl onal anti-gp38k antibody. Because gp38k expression is also correlated with changes in culture morphology, we also assessed its ability to act as an ag onist of HUVEC morphology using cultures growing on Matrigel. We report tha t gp38k stimulates endothelial cell tubulogenesis in this assay system. The se results provide the first evidence that gp38k may function in angiogenes is by stimulating the migration and reorganization of vascular endothelial cells, (C) 1999 Academic Press.