Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1993 May;67(5):939–944. doi: 10.1038/bjc.1993.174

Interleukin-6 cDNA transfected Lewis lung carcinoma cells show unaltered net tumour growth rate but cause weight loss and shortened survival in syngeneic mice.

Y Ohe 1, E R Podack 1, K J Olsen 1, Y Miyahara 1, K Miura 1, H Saito 1, Y Koishihara 1, Y Ohsugi 1, T Ohira 1, K Nishio 1, et al.
PMCID: PMC1968462  PMID: 8494727

Abstract

HuIL-6 cDNA, cloned into a neomycin resistant conferring expression vector, BMGNeo, was transfected into Lewis Lung Carcinoma (LLC) cells. LLC cells (5 x 10(6) ml-1) transfected with IL-6 cDNA (LLC-IL6) secreted IL-6 into the culture supernatant at a concentration of 9.9 ng ml-1 within 48 h. When 1,000,000 of untransfected LLC, BMGNeo vector transfected LLC (LLC-Neo) or LLC-IL6 cells were transplanted into C57BL/6 mice subcutaneously, the mean +/- s.d. of survival times of these mice were 33.3 +/- 9.7, 34.3 +/- 7.1 and 17.0 +/- 3.1 days, respectively. The survival time of LLC-IL6 cells transplanted mice was significantly shorter than that of LLC (P < 0.01) or LLC-Neo (P < 0.01) cells transplanted mice without a measurable difference of tumour size. Plasma concentration of IL-6 steadily increased in LLC-IL6 transplanted mice. Body weight and serum albumin were significantly lower in LLC-IL6 transplanted mice than in LLC transplanted mice. Mouse IL-1 alpha and mouse TNF-alpha were not detected in the plasma of LLC-IL6 transplanted mice. These data suggested that secretion of IL-6 from LLC cells was unable to alter net tumour growth rate but rather caused a state similar to cachexia without detectable increase of IL-1 alpha and TNF-alpha in the plasma. This state may be responsible for the shortened survival of LLC-IL6 tumour-bearing mice.

Full text

PDF
939

Images in this article

942Figure 6
on p.942

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andus T., Geiger T., Hirano T., Northoff H., Ganter U., Bauer J., Kishimoto T., Heinrich P. C. Recombinant human B cell stimulatory factor 2 (BSF-2/IFN-beta 2) regulates beta-fibrinogen and albumin mRNA levels in Fao-9 cells. FEBS Lett. 1987 Aug 31;221(1):18–22. doi: 10.1016/0014-5793(87)80344-7. [DOI] [PubMed] [Google Scholar]
  2. Asher A. L., Mulé J. J., Kasid A., Restifo N. P., Salo J. C., Reichert C. M., Jaffe G., Fendly B., Kriegler M., Rosenberg S. A. Murine tumor cells transduced with the gene for tumor necrosis factor-alpha. Evidence for paracrine immune effects of tumor necrosis factor against tumors. J Immunol. 1991 May 1;146(9):3227–3234. [PMC free article] [PubMed] [Google Scholar]
  3. Bataille R., Jourdan M., Zhang X. G., Klein B. Serum levels of interleukin 6, a potent myeloma cell growth factor, as a reflect of disease severity in plasma cell dyscrasias. J Clin Invest. 1989 Dec;84(6):2008–2011. doi: 10.1172/JCI114392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Black K., Garrett I. R., Mundy G. R. Chinese hamster ovarian cells transfected with the murine interleukin-6 gene cause hypercalcemia as well as cachexia, leukocytosis and thrombocytosis in tumor-bearing nude mice. Endocrinology. 1991 May;128(5):2657–2659. doi: 10.1210/endo-128-5-2657. [DOI] [PubMed] [Google Scholar]
  5. Blankenstein T., Qin Z. H., Uberla K., Müller W., Rosen H., Volk H. D., Diamantstein T. Tumor suppression after tumor cell-targeted tumor necrosis factor alpha gene transfer. J Exp Med. 1991 May 1;173(5):1047–1052. doi: 10.1084/jem.173.5.1047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Colombo M. P., Ferrari G., Stoppacciaro A., Parenza M., Rodolfo M., Mavilio F., Parmiani G. Granulocyte colony-stimulating factor gene transfer suppresses tumorigenicity of a murine adenocarcinoma in vivo. J Exp Med. 1991 Apr 1;173(4):889–897. doi: 10.1084/jem.173.4.889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Felgner P. L., Gadek T. R., Holm M., Roman R., Chan H. W., Wenz M., Northrop J. P., Ringold G. M., Danielsen M. Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7413–7417. doi: 10.1073/pnas.84.21.7413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Galfre G., Howe S. C., Milstein C., Butcher G. W., Howard J. C. Antibodies to major histocompatibility antigens produced by hybrid cell lines. Nature. 1977 Apr 7;266(5602):550–552. doi: 10.1038/266550a0. [DOI] [PubMed] [Google Scholar]
  9. Gansbacher B., Bannerji R., Daniels B., Zier K., Cronin K., Gilboa E. Retroviral vector-mediated gamma-interferon gene transfer into tumor cells generates potent and long lasting antitumor immunity. Cancer Res. 1990 Dec 15;50(24):7820–7825. [PubMed] [Google Scholar]
  10. Gelin J., Moldawer L. L., Lönnroth C., Sherry B., Chizzonite R., Lundholm K. Role of endogenous tumor necrosis factor alpha and interleukin 1 for experimental tumor growth and the development of cancer cachexia. Cancer Res. 1991 Jan 1;51(1):415–421. [PubMed] [Google Scholar]
  11. Hill R. J., Warren M. K., Levin J. Stimulation of thrombopoiesis in mice by human recombinant interleukin 6. J Clin Invest. 1990 Apr;85(4):1242–1247. doi: 10.1172/JCI114559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hirano T., Yasukawa K., Harada H., Taga T., Watanabe Y., Matsuda T., Kashiwamura S., Nakajima K., Koyama K., Iwamatsu A. Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature. 1986 Nov 6;324(6092):73–76. doi: 10.1038/324073a0. [DOI] [PubMed] [Google Scholar]
  13. Karasuyama H., Melchers F. Establishment of mouse cell lines which constitutively secrete large quantities of interleukin 2, 3, 4 or 5, using modified cDNA expression vectors. Eur J Immunol. 1988 Jan;18(1):97–104. doi: 10.1002/eji.1830180115. [DOI] [PubMed] [Google Scholar]
  14. Kitahara M., Kishimoto S., Hirano T., Kishimoto T., Okada M. The in vivo anti-tumor effect of human recombinant interleukin-6. Jpn J Cancer Res. 1990 Oct;81(10):1032–1038. doi: 10.1111/j.1349-7006.1990.tb03342.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Luger T. A., Krutmann J., Kirnbauer R., Urbanski A., Schwarz T., Klappacher G., Köck A., Micksche M., Malejczyk J., Schauer E. IFN-beta 2/IL-6 augments the activity of human natural killer cells. J Immunol. 1989 Aug 15;143(4):1206–1209. [PubMed] [Google Scholar]
  16. Lönnroth C., Moldawer L. L., Gelin J., Kindblom L., Sherry B., Lundholm K. Tumor necrosis factor-alpha and interleukin-1 alpha production in cachectic, tumor-bearing mice. Int J Cancer. 1990 Nov 15;46(5):889–896. doi: 10.1002/ijc.2910460523. [DOI] [PubMed] [Google Scholar]
  17. Merriman R. L., Shackelford K. A., Tanzer L. R., Campbell J. B., Bemis K. G., Matsumoto K. Drug treatments for metastasis of the Lewis lung carcinoma: lack of correlation between inhibition of lung metastasis and survival. Cancer Res. 1989 Aug 15;49(16):4509–4516. [PubMed] [Google Scholar]
  18. Mizuno M., Yoshida J., Sugita K., Inoue I., Seo H., Hayashi Y., Koshizaka T., Yagi K. Growth inhibition of glioma cells transfected with the human beta-interferon gene by liposomes coupled with a monoclonal antibody. Cancer Res. 1990 Dec 15;50(24):7826–7829. [PubMed] [Google Scholar]
  19. Mulé J. J., McIntosh J. K., Jablons D. M., Rosenberg S. A. Antitumor activity of recombinant interleukin 6 in mice. J Exp Med. 1990 Mar 1;171(3):629–636. doi: 10.1084/jem.171.3.629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Oliff A., Defeo-Jones D., Boyer M., Martinez D., Kiefer D., Vuocolo G., Wolfe A., Socher S. H. Tumors secreting human TNF/cachectin induce cachexia in mice. Cell. 1987 Aug 14;50(4):555–563. doi: 10.1016/0092-8674(87)90028-6. [DOI] [PubMed] [Google Scholar]
  21. SUGIURA K., STOCK C. C. Studies in a tumor spectrum. III. The effect of phosphoramides on the growth of a variety of mouse and rat tumors. Cancer Res. 1955 Jan;15(1):38–51. [PubMed] [Google Scholar]
  22. 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]
  23. Teng M. N., Park B. H., Koeppen H. K., Tracey K. J., Fendly B. M., Schreiber H. Long-term inhibition of tumor growth by tumor necrosis factor in the absence of cachexia or T-cell immunity. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3535–3539. doi: 10.1073/pnas.88.9.3535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Van Snick J. Interleukin-6: an overview. Annu Rev Immunol. 1990;8:253–278. doi: 10.1146/annurev.iy.08.040190.001345. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES