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Adherence of Human Erythroleukemia Cells Inhibits Proliferation without Inducing Differentiation¹

Laboratoire d’étude de la différenciation et de l’adhérence cellulaires, UMR Centre National de la Recherche Scientifique/UJF 5538, Institut Albert Bonniot, Faculté de Médecine Domaine de la Merci, 38706 La Tronche Cedex, France

Abstract

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 5ß1, and this receptor acted synergetically with 4ß1. Integrin engagement induced cell growth arrest through mitogen-activated protein kinase inactivation. Such down-regulation of the mitogen-activated protein kinase pathway by integrin engagement was suggested as a megakaryocytic-platelet lineage specificity. This signaling was not restricted to a peculiar integrin but was proposed as a general mechanism in these cells.