Crucial role of phosphatase CD45 in determining signaling and proliferation of human myeloma cells.
In multiple myeloma, a large number of growth factors (IL-6, IGF-1, FGF, HGF and HB-EGF) are involved in promoting myeloma cell growth. In the present study, a serum-free, cytokine-free, collagen-based assay, which does not allow the generation of spontaneous myeloma colonies, was used to identify the clonogenic growth factors for fourteen myeloma cell lines. IL-6 is the only clonogenic factor able to stimulate both CD45+ and CD45- myeloma cell lines, generating myeloma colonies from 10 out of 14 myeloma cell lines. Using a pharmacological Erk inhibitor, we show that the Erk/MAPK pathway is involved in IL-6-induced clonogenicity of CD45+, but not CD45- myeloma cell lines. In contrast to IL-6, the other growth factors (IGF-1, FGF, HGF and HB-EGF) stimulate only some myeloma cell lines, but always CD45-, and less effectively than IL-6. Among them, IGF-1 is the most potent, generating myeloma colonies from five out of eight CD45- myeloma cell lines. Finally, the capacity of IGF-1 and FGF to stimulate the clonogenicity of CD45- myeloma cells correlates with their ability to stimulate the Erk/MAPK pathway. We conclude that CD45 expression plays a crucial role in determining signaling and proliferation of human myeloma cell responses to IL-6, IGF-1 and other growth factors. The poor outcome of CD45- myeloma patients could be related to the capacity of CD45-myeloma cells to take advantage of multiple growth factors.
Collette
Madeleine
M
INSERM, U601, Département de Recherche en Cancérologie, LNC Label, Institut de Biologie, 9 quai Moncousu, 44000 Nantes, France.
Descamps
Géraldine
G
Pellat-Deceunynck
Catherine
C
Bataille
Régis
R
Amiot
Martine
M
D002455:Cell Division; D002460:Cell Line; D049109:Cell Proliferation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D009101:Multiple Myeloma / Q000201:enzymology* / Q000473:pathology*; D015398:Signal Transduction / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay / Q000379:methods