Distinct IL-6 signal transduction leads to growth arrest and death in B cells or growth promotion and cell survival in myeloma cells.
In B cell development, interleukin-6 (IL-6) induces terminal maturation of B lymphocytes into antibody producing plasma cells. Terminal differentiated B cells cell cycle arrest and death follows. In contrast, IL-6 acts as a growth factor for malignant myeloma plasma cells and in some cases protects them from therapeutic treatment. In this study, we examined two cell lines that show different responses to IL-6. Lymphoblastoid CESS cells respond to IL-6 by terminally differentiating into antibody producing plasma cells, cell cycle arrest, and undergo cell death. Continuous addition of IL-6 to these cells induces transient activation of STAT3, SHP-2 phosphorylation, and does not alter bcl-X(L) and c-myc expression. In contrast, the myeloma line ANBL6 proliferates when stimulated with IL-6 and this correlates with prolonged STAT3 activation and up-regulation of bcl-X(L) and c-myc. Interestingly, gp130-associated SHP-2 phosphorylation was detected in the IL-6-induced CESS cells but not myeloma cell lines. The data show a very distinct IL-6 signal transduction and kinetics in these cell lines and the distinct molecular events correlate closely to the cell fate of the lymphoblast and myeloma cell lines.
Cheung
W-C
WC
Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
Van Ness
B
B
D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000378:metabolism; D015850:Interleukin-6 / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D019947:Receptors, Interleukin-6 / Q000032:analysis / Q000378:metabolism; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D051020:bcl-X Protein
D004268:DNA-Binding Proteins; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; D051020:bcl-X Protein; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases