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...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 1998-03, Vol.244 (3), p.745-750
Main Authors: Hamada, Koichi, Nakamura, Hitoshi, Oda, Tsukasa, Hirano, Tetsuo, Shimizu, Noriaki, Utiyama, Hiroyasu
Format: Article
Language:English
Subjects:
Apoptosis
CD18 Antigens - metabolism
Cell Adhesion
Cell Survival
Humans
Integrins - metabolism
Leukemia
Lysophospholipids
Macrophage-1 Antigen - metabolism
Monocytes - drug effects
Phorbol 12,13-Dibutyrate - pharmacology
Sphingosine - analogs & derivatives
Sphingosine - pharmacology
Tumor Cells, Cultured
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Summary: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.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.1998.8328