Adherence of Human Erythroleukemia Cells Inhibits Proliferation without Inducing Differentiation

To investigate the effect of extracellular matrix molecules in the megakaryocytic lineage, we studied the role of integrin engagement in the proliferation and differentiation of human erythroleukemia (HEL) cells. HEL cells grew in suspension, but their adherence depended upon the presence of matrix proteins or protein kinase C signaling. Adherence by itself did not trigger commitment of these cells but accelerated phorbol 12-myristate 13-acetate-induced differentiation. HEL cells adhered to fibronectin mainly through a5b1, and this receptor acted synergetically with a4b1. Integrin engagement induced cell growth arrest through mitogen-activated protein kinase inactivation. Such down-regulation of the mitogenactivated protein kinase pathway by integrin engagement was suggested as a megakaryocyticplatelet lineage specificity. This signaling was not restricted to a peculiar integrin but was proposed as a general mechanism in these cells.