Abstract
Murine plasmacytomas show a striking dependence on interleukin 6 (IL-6) for their growth in vitro. Here, we present evidence suggesting that IL- 6 also plays an essential role in the in vivo development of these tumors. This conclusion is based on the finding that the tumorigenicity of an IL-6-dependent plasmacytoma cell line was increased approximately 100-fold on transfection with an IL-6 expression vector, whereas it was inhibited in animals treated with monoclonal antibodies capable of blocking the binding of IL-6 to its receptor. Injection of these antibodies 1 d before tumor challenge protected greater than 50% of the mice and retarded tumor growth in all animals. Tumors arising in antibody-treated mice retained their IL-6 dependence in vitro, suggesting that the level of protection could be improved if stronger IL-6 antagonists were available.
Full Text
The Full Text of this article is available as a PDF (324.8 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bergui L., Schena M., Gaidano G., Riva M., Caligaris-Cappio F. Interleukin 3 and interleukin 6 synergistically promote the proliferation and differentiation of malignant plasma cell precursors in multiple myeloma. J Exp Med. 1989 Aug 1;170(2):613–618. doi: 10.1084/jem.170.2.613. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Muraguchi A., Hirano T., Tang B., Matsuda T., Horii Y., Nakajima K., Kishimoto T. The essential role of B cell stimulatory factor 2 (BSF-2/IL-6) for the terminal differentiation of B cells. J Exp Med. 1988 Feb 1;167(2):332–344. doi: 10.1084/jem.167.2.332. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nordan R. P., Potter M. A macrophage-derived factor required by plasmacytomas for survival and proliferation in vitro. Science. 1986 Aug 1;233(4763):566–569. doi: 10.1126/science.3726549. [DOI] [PubMed] [Google Scholar]
- POTTER M., BOYCE C. R. Induction of plasma-cell neoplasms in strain BALB/c mice with mineral oil and mineral oil adjuvants. Nature. 1962 Mar 17;193:1086–1087. doi: 10.1038/1931086a0. [DOI] [PubMed] [Google Scholar]
- Shimizu S., Yoshioka R., Hirose Y., Sugai S., Tachibana J., Konda S. Establishment of two interleukin 6 (B cell stimulatory factor 2/interferon beta 2)-dependent human bone marrow-derived myeloma cell lines. J Exp Med. 1989 Jan 1;169(1):339–344. doi: 10.1084/jem.169.1.339. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Suematsu S., Matsuda T., Aozasa K., Akira S., Nakano N., Ohno S., Miyazaki J., Yamamura K., Hirano T., Kishimoto T. IgG1 plasmacytosis in interleukin 6 transgenic mice. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7547–7551. doi: 10.1073/pnas.86.19.7547. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tohyama N., Karasuyama H., Tada T. Growth autonomy and tumorigenicity of interleukin 6-dependent B cells transfected with interleukin 6 cDNA. J Exp Med. 1990 Feb 1;171(2):389–400. doi: 10.1084/jem.171.2.389. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Van Snick J., Cayphas S., Szikora J. P., Renauld J. C., Van Roost E., Boon T., Simpson R. J. cDNA cloning of murine interleukin-HP1: homology with human interleukin 6. Eur J Immunol. 1988 Feb;18(2):193–197. doi: 10.1002/eji.1830180202. [DOI] [PubMed] [Google Scholar]
- Van Snick J., Vink A., Cayphas S., Uyttenhove C. Interleukin-HP1, a T cell-derived hybridoma growth factor that supports the in vitro growth of murine plasmacytomas. J Exp Med. 1987 Mar 1;165(3):641–649. doi: 10.1084/jem.165.3.641. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vink A., Coulie P. G., Wauters P., Nordan R. P., Van Snick J. B cell growth and differentiation activity of interleukin-HP1 and related murine plasmacytoma growth factors. Synergy with interleukin 1. Eur J Immunol. 1988 Apr;18(4):607–612. doi: 10.1002/eji.1830180418. [DOI] [PubMed] [Google Scholar]