Involvement of Mac-1-mediated adherence and sphingosine 1-phosphate in survival of phorbol ester-treated U937 cells.
Phorbol esters exert a dual function in human leukemia cells, induction of differentiation and activation of integrin-mediated functions. Here we have shown that the plastic adherence of phorbol ester-treated U937 cells is mediated by expression of integrin Mac-1 (CD11b/CD18) on the cell surface and that these adherent cells exhibit anoikis (apoptosis when adherent cells are detached or adherence is inhibited). We used U937-derived clones overexpressing either antisense RNAs antisense to CD11b and CD18 mRNAs or mRNA from a truncated mutant CD11b gene. We have also shown that apoptosis in non-adherent cells or anoikis was mediated by sphingosine and that survival of adherent cells was achieved by a shift of the dynamic balance between sphingosine and sphingosine 1-phosphate toward the latter by adherence-activated sphingosine 1-kinase.
Hamada
K
K
Life Science Group, Faculty of Integrated Arts and Sciences, Hiroshima University, Japan.
Nakamura
H
H
Oda
T
T
Hirano
T
T
Shimizu
N
N
Utiyama
H
H
D017209:Apoptosis; D018821:CD18 Antigens / Q000378:metabolism*; D002448:Cell Adhesion; D002470:Cell Survival; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D007938:Leukemia; D008246:Lysophospholipids; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D018821:CD18 Antigens; D016023:Integrins; D008246:Lysophospholipids; D016177:Macrophage-1 Antigen; C060506:sphingosine 1-phosphate; D015240:Phorbol 12,13-Dibutyrate; D013110:Sphingosine