A role for IFN-lambda1 in multiple myeloma B cell growth.
Multiple myeloma (MM) is a progressive disease that results from dysregulated proliferation of plasma cells. Although, causative factors such as genetic events and altered expression of anti-apoptotic factors have been described in a number of patients, the mechanistic details that drive myeloma development and continued growth of malignant cells remain largely undefined. Numerous growth factors, including interleukin (IL)-6, Insulin-like growth factor-1 and IL-10 have been shown to promote growth of MM cells suggesting a significant role for cytokines in this disease. Interferon (IFN)-lambda1 is a new member of the Class II cytokine family that, similar to IFN-alpha, has been shown to mediate viral immunity. In light of data supporting a role for cytokines in myeloma, we investigated the significance of IFN-lambda1 on myeloma cell biology. Our studies show for the first time that myeloma cells bind to soluble IFN-lambda1, and that IFN-lambda1 induces myeloma cell growth and protects against dexamethasone-induced cell death. Our data also show that IFN-lambda1 induces phosphorylation of STAT1, STAT3 and Erk. Taken together, our results suggest that IFN-lambda1 may regulate myeloma cell biology and could prove to be therapeutically important.
Novak
A J
AJ
Department of Medicine, Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA.
Grote
D M
DM
Ziesmer
S C
SC
Rajkumar
V
V
Doyle
S E
SE
Ansell
S M
SM
D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009101:Multiple Myeloma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D010766:Phosphorylation; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000095022:Interferon Lambda
D003907:Dexamethasone; D048049:Extracellular Signal-Regulated MAP Kinases; D005938:Glucocorticoids; D007372:Interferons; D007378:Interleukins; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C494079:STAT1 protein, human; C494086:STAT3 protein, human