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 alpha5beta1, and this receptor acted synergetically with alpha4beta1. 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.
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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, La Tronche, France. annie.molla@ujf-grenoble.fr
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D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000502:physiology; D005353:Fibronectins; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000502:physiology; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009363:Neoplasm Proteins / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D017469:Receptors, Fibronectin / Q000502:physiology; D016201:Receptors, Lymphocyte Homing / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D039041:Integrin alpha4beta1; D016023:Integrins; D009363:Neoplasm Proteins; D017469:Receptors, Fibronectin; D016201:Receptors, Lymphocyte Homing; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D013755:Tetradecanoylphorbol Acetate