THE EXTRACELLULAR-MATRIX AS A CELL-SURVIVAL FACTOR

Programmed cell death (PCD) or apoptosis is a naturally occurring cell suicide pathway induced in a variety of cell types. In many cases, PC D is induced by the withdrawal of specific hormones or growth factors that function as survival factors. In this study, we have investigated the potential role of the extracellular matrix (ECM) as a cell surviv al factor. Our results indicate that in the absence of any ECM interac tions, human endothelial cells rapidly undergo PCD, as determined by c ell morphology, nuclei fragmentation, DNA degradation, protein cross-l inking, and the expression of the PCD-specific gene TRPM-2. PCD was bl ocked by plating cells on an immobilized integrin beta1 antibody but n ot by antibodies to either the class I histocompatability antigen (HLA ) or vascular cell adhesion molecule-1 (VCAM-1), suggesting that integ rin-mediated signals were required for maintaining cell viability. Tre atment of the cells in suspension with the tyrosine phosphatase inhibi tor sodium orthovanadate also blocked PCD. When other cell types were examined, some, but not all, underwent rapid cell death when deprived of adhesion to the ECM. These results suggest that in addition to regu lating cell growth and differentiation, the ECM also functions as a su rvival factor for many cell types.