Acquisition of growth autonomy and tumorigenicity by an interleukin 6-dependent human myeloma cell line transfected with interleukin 6 cDNA

In human multiple myeloma, an autocrine growth mechanism through interleukin 6 (IL-6) has been advocated. However, growth of myeloma cells in vitro is poor except for established cell lines, and IL-6 autocrine growth is quite rare in myeloma cell lines. In the present study, we devised a model of IL-6 autocrine growth in vitro by transfecting IL-6 cDNA into a human myeloma cell line that had a proliferative response to IL-6 but did not produce IL-6. After IL-6 transfection, the cells proliferated in culture media without IL-6, and their growth rate was elevated at higher cell densities. IL-6 was detected by enzyme-linked immunosorbent assay in the culture media of the transfectants. IL-6 mRNA was distinctly expressed in these cells when analyzed by Northern blotting. The growth of the transfectants was definitely inhibited by anti-IL-6 or anti-IL-6 receptor monoclonal antibodies. Furthermore, the transfectants were successfully transplanted to nude mice. These results indicate that the myeloma cells obtained growth autonomy in vitro through IL-6 and tumorigenicity in vivo, after IL-6 transfection.