Lymphoma and myeloma cell resistance to cytotoxic agents and ionizing radiations is not affected by exposure to anti-IL-6 antibody - Archive ouverte HAL Access content directly
Journal Articles PLoS ONE Year : 2009

Lymphoma and myeloma cell resistance to cytotoxic agents and ionizing radiations is not affected by exposure to anti-IL-6 antibody

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Abstract

Background: Production of high levels of IL-6 is often correlated with resistance to cytotoxics or ionizing radiations, in cancer cell lines as in various cancer patients. We investigated whether monoclonal antibodies directed against IL-6 may enable to reverse resistance of cancer cell lines. Methodology/Principal Findings: We exposed ten haematological cancer cells from lymphoma, myeloma or leukemia origins to cytotoxics or ionizing radiations and assessed the effects of anti-IL-6 antibody addition on cell proliferation, apoptosis or IL-6 signaling. A strong correlation between IL-6 secretion, measured by ELISA, and resistance to doxorubicin as ionizing radiations was observed in the multiple myeloma U266 and the Burkitt's lymphoma Daudi and Namalwa cells. Although an anti-IL-6 antibody combined to both treatments efficiently blocked IL-6 signaling in U266 cells, expressing the IL-6 receptor gp80, it did not increase treatment-induced anti-proliferative and pro-apoptotic effects on these cells, as well as on Daudi and Namalwa cells. This lack of effect could be related to diverse factors: 1) a higher release of the soluble form of IL-6 receptor gp80 in response to doxorubicin and irradiation from all cell lines, 2) an impaired level of the IL-6 pathway inhibitor SOCS3 in Daudi cells, and 3) an increased release of IL-10 and TNFα, two cytokines involved in cell radio- and chemoresistance. Conclusions/significance: These data support the fact that IL-6 is not the preponderant actor of cell resistance to cytotoxics and ionizing radiations, which seems to be regulated by a complex network of proteins.
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Dates and versions

inserm-00441337 , version 1 (15-12-2009)

Identifiers

  • HAL Id : inserm-00441337 , version 1
  • PUBMED : 19956602

Cite

Angélique Gougelet, Adeline Mansuy, Jean-Yves Blay, Laurent Alberti, Claudine Vermot-Desroches. Lymphoma and myeloma cell resistance to cytotoxic agents and ionizing radiations is not affected by exposure to anti-IL-6 antibody: IL-6 and resistance to cytotoxics. PLoS ONE, 2009, http://dx.plos.org/10.1371/journal.pone.0008026. ⟨inserm-00441337⟩
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