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.
Okuno
Y
Y
2nd Department of Internal Medicine, Kyoto University, Japan.
Takahashi
T
T
Suzuki
A
A
Fukumoto
M
M
Nakamura
K
K
Fukui
H
H
Koishihara
Y
Y
Ohsugi
Y
Y
Imura
H
H
D000818:Animals; D002455:Cell Division; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000502:physiology*; D051379:Mice; D009101:Multiple Myeloma / Q000473:pathology*; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000235:genetics; D011971:Receptors, Immunologic / Q000502:physiology; D019947:Receptors, Interleukin-6; D014162:Transfection; D014407:Tumor Cells, Cultured
D015850:Interleukin-6; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6