We explored the molecular mechanisms involved in the establishement of CMA-03/06, an IL-6-independent variant of the multiple myeloma cell line CMA-03 previously generated in our Institution. CMA-03/06 cells grow in the absence of IL-6 with a doubling time comparable with that of CMA-03 cells; neither the addition of IL6 (IL-6) to the culture medium nor co-culture with multipotent mesenchymal stromal cells increases the proliferation rate, although they maintain the responsiveness to IL-6 stimulation as demonstrated by STAT1, STAT3, and STAT5 induction. IL-6 independence of CMA-03/06 cells is not apparently due to the development of an autocrine IL-6 loop, nor to the observed moderate constitutive activation of STAT5 and STAT3, since STAT3 silencing does not affect cell viability or proliferation. When compared to the parental cell line, CMA-03/06 cells showed an activated pattern of the NF-κB pathway. This finding is supported by gene expression profiling (GEP) analysis identifying an appreciable fraction of modulated genes (28/308) in the CMA-03/06 subclone reported to be involved in this pathway. Furthermore, although more resistant to apoptotic stimuli compared to the parental cell line, CMA-03/06 cells display a higher sensibility to NF-κB inhibition induced by bortezomib. Finally, GEP analysis suggests an involvement of a number of cytokines, which might contribute to IL-6 independence of CMA-03/06 by stimulating growth and antiapoptotic processes. In conclusion, the parental cell-line CMA-03 and its variant CMA-03/06 represent a suitable model to further investigate molecular mechanisms involved in the IL-6-independent growth of myeloma cells.
Molecular events underlying interleukin-6 independence in a subclone of the CMA-03 multiple myeloma cell line / D. Verdelli, L. Nobili, K. Todoerti, L. Mosca, S. Fabris, M. D'Anca, E. Pellegrino, R. Piva, G. Inghirami, C. Capelli, M. Introna, L. Baldini, R. Chiaramonte, L. Lombardi, A. Neri. - In: GENES, CHROMOSOMES & CANCER. - ISSN 1045-2257. - 53:2(2014 Feb), pp. 154-167.
|Titolo:||Molecular events underlying interleukin-6 independence in a subclone of the CMA-03 multiple myeloma cell line|
VERDELLI, DONATA (Primo)
NOBILI, RITA LUCIA (Secondo)
NERI, ANTONINO (Ultimo)
|Settore Scientifico Disciplinare:||Settore MED/15 - Malattie del Sangue|
|Data di pubblicazione:||feb-2014|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1002/gcc.22127|
|Appare nelle tipologie:||01 - Articolo su periodico|