Induced cell surface expression of functional alpha 2 beta 1 integrin during megakaryocytic differentiation of K562 leukemic cells.
The pluripotential hematopoietic cell line K562 was studied as a model of inducible integrin expression accompanying differentiation. Differentiation along the megakaryocytic pathway was induced with phorbol 12,13-dibutyrate and differentiation along the erythroid pathway with hemin. Induction of megakaryocytic differentiation was associated with changes in cell morphology and with increased cell-cell and cell-substrate adhesion and spreading. Erythroid differentiation was not associated with changes in morphology or adhesion. Cell surface expression of the IIb-IIIa and alpha 2 beta 1 integrins increased markedly with phorbol treatment but decreased with hemin treatment. Phorbol-treated K562 cells, but not control cells or hemin-treated cells, adhered to collagen substrates in a Mg(2+)-dependent manner which was specifically inhibited by a monoclonal antibody directed against the alpha 2 beta 1 integrin. Northern blot analysis revealed that megakaryocytic differentiation of K562 cells was accompanied by de novo expression of the alpha 2 integrin mRNA with no change in the level of mRNA for the beta 1 subunit. K562 cells provide a model of differentiation-dependent, regulated integrin expression in which expression is up- or down-regulated depending upon the differentiation pathway selected.
Burger
S R
SR
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
Zutter
M M
MM
Sturgill-Koszycki
S
S
Santoro
S A
SA
D000906:Antibodies; D000911:Antibodies, Monoclonal; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D006427:Hemin / Q000494:pharmacology*; D006801:Humans; D016023:Integrins / Q000096:biosynthesis*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D008533:Megakaryocytes / Q000166:cytology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*
D000906:Antibodies; D000911:Antibodies, Monoclonal; D016023:Integrins; D015240:Phorbol 12,13-Dibutyrate; D006427:Hemin