Abstract
Although IFN-α is commonly used as maintenance treatment for multiple myeloma patients, its effectiveness is varied. In this study, we have used a panel of IL-6 responsive myeloma cell lines that vary remarkably in responsiveness to IFN-α. Three cell lines were growth arrested by IFN-α; however, IFN-α significantly stimulated growth of the fourth cell line, KAS- 6/1. Our studies have focused on elucidating the mechanism of differential IFN-α responsiveness. First, we have shown that IFN-α-stimulated growth of the KAS-6/1 cells did not result from induction of autocrine IL-6 expression. Second, analysis of Stats 1; 2, and 3 and IFN regulatory factor-1 (IRF-1) and IRF-2 activation failed to reveal differences between the IFN-α growth- arrested or growth-stimulated cells. Third, although IFN-α treatment of the IFN-α growth-inhibited cell lines reduced IL-6 receptor (IL-6R) expression, IFN-α also reduced KAS-6/1 IL-6R expression. Finally, although IFN-α treatment reduced IL-6R numbers on each cell line, analysis of Stat protein activation revealed that the receptors were still functional. We conclude that myeloma cell responsiveness to IFN-α is heterogeneous and that mechanisms of IFN-α-mediated growth inhibition other than IL-6R downregulation must exist in myeloma. Identification of these mechanisms may allow development of agents that are more universally effective than IFN-α.
Original language | English (US) |
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Pages (from-to) | 447-456 |
Number of pages | 10 |
Journal | Journal of Clinical Investigation |
Volume | 99 |
Issue number | 3 |
DOIs | |
State | Published - Feb 1 1997 |
Keywords
- Autocrine IL-6
- Cell cycle
- Growth factor
- IFN-α
- Myeloma
ASJC Scopus subject areas
- General Medicine