The extracellular matrix as a cell survival factor.

TLDR

Programmed cell death is triggered when cells lose survival signals such as hormones or growth factors. The study examined whether the extracellular matrix can act as a survival factor for cells. The authors found that loss of ECM interactions causes rapid apoptosis in human endothelial cells, which is prevented by integrin‑beta1 engagement or tyrosine‑phosphatase inhibition, and that many cell types similarly require ECM adhesion for survival.

Abstract

Programmed cell death (PCD) or apoptosis is a naturally occurring cell suicide pathway induced in a variety of cell types. In many cases, PCD 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 survival factor. Our results indicate that in the absence of any ECM interactions, human endothelial cells rapidly undergo PCD, as determined by cell morphology, nuclei fragmentation, DNA degradation, protein cross-linking, and the expression of the PCD-specific gene TRPM-2. PCD was blocked by plating cells on an immobilized integrin beta 1 antibody but not by antibodies to either the class I histocompatibility antigen (HLA) or vascular cell adhesion molecule-1 (VCAM-1), suggesting that integrin-mediated signals were required for maintaining cell viability. Treatment of the cells in suspension with the tyrosine phosphatase inhibitor 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 regulating cell growth and differentiation, the ECM also functions as a survival factor for many cell types.