Skip to main content
PMC home page
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1997 Oct;88(10):953–958. doi: 10.1111/j.1349-7006.1997.tb00314.x

Expression of Interleukin‐6 and Its Effect on the Cell Growth of Gastric Carcinoma Cell Lines

Reiko Ito 1,2, Wataru Yasui 1, Hiroki Kuniyasu 1, Hiroshi Yokozaki 1, Eiichi Tahara 1,✉
PMCID: PMC5921276  PMID: 9414656

Abstract

The expression and the effect of IL‐6 were examined in human gastric carcinoma cell lines to determine whether IL‐6 serves as a growth stimulator. The expression of IL‐6 mRNA was detected in three (TMK‐1, MKN‐1, MKN‐7) of 8 gastric carcinoma cell lines. All three cell lines secreted IL‐6 into the culture fluid, in large amounts in the cases of MKN‐1 and MKN‐7 cells. Scatchard plot analysis of IL‐6 binding revealed that MKN‐1 and MKN‐7 cells had both high‐ and low‐affinity receptors. Cell growth of MKN‐1 and MKN‐7 cells was stimulated by IL‐6, while anti‐IL‐6 antibody inhibited growth. The expression of IL‐la mRNA by these three cell lines was induced by IL‐6. IL‐la increased the expression of mRNA for IL‐6 by TMK‐1 cells. These findings indicate that IL‐6 induced by IL‐la is an autocrine growth factor for some gastric carcinomas

Keywords: IL‐6, Gastric carcinoma cell line, Autocrine, Cytokine

Full Text

The Full Text of this article is available as a PDF (324.8 KB).

REFERENCES

  • 1. ) Tahara , E.Molecular mechanism of stomach carcino‐genesis . J. Cancer Res. Clin. Oncol. , 119 , 1 – 8 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) Tahara , E. , Sumiyoshi , H. , Hata , J. , Yasui , W. , Taniyama , K. , Hayashi , T. , Nagae , S. and Sakamoto , S.Human epidermal growth factor in gastric carcinoma as a biologic marker of high malignancy . Jpn. J. Cancer Res. (Gann) , 77 , 145 – 152 ( 1986. ). [PubMed] [Google Scholar]
  • 3. ) Yasui , W. , Sumiyoshi , H. , Hata , J. , Kameda , T. , Ochiai , A. , Ito , H. and Tahara , E.Expression of epidermal growth factor receptor in human gastric and colonic carcinomas . Cancer Res. , 48 , 137 – 141 ( 1988. ). [PubMed] [Google Scholar]
  • 4. ) Yoshida , K. , Tsujino , T. , Yasui , W. , Kameda , T. , Sano , T. , Nakayama , H. , Toge , T. and Tahara , E.Induction of growth factor‐receptor and metalloproteinase genes by epidermal growth factor and/or transforming growth factor‐α in human gastric carcinoma cell line MKN‐28 . Jpn. J. Cancer Res. , 81 , 793 – 798 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5. ) Ito , R. , Kitadai , Y. , Kyo , E. , Yokozaki , H. , Yasui , W. , Yamashita , U. , Nikai , H. and Tahara , E.Interleukin lα acts as an autocrine growth stimulator for human gastric carcinoma cells . Cancer Res. , 53 , 4102 – 4106 ( 1993. ). [PubMed] [Google Scholar]
  • 6. ) Hirano , T. , Taga , T. , Nakano , N. , Yasukawa , K. , Kashiwamura , S. , Shimizu , K. , Nakajima , K. , Pyun , K. H. and Kishimoto , T.Purification to homogeneity and characterization of human B‐cell differentiation factor (BCDF or BSFp‐2) . Proc. Natl. Acad. Sci. USA , 82 , 5490 – 5494 ( 1985. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7. ) Takai , Y. , Wong , G. G. , Clark , S. C. , Burakoff , S. F. and Herrmann , S. H.B cell stimulatory factor‐2 is involved in the differentiation of cytotoxic T lymphocytes . J. Immunol. , 140 , 508 – 512 ( 1988. ). [PubMed] [Google Scholar]
  • 8. ) Gauldie , J. , Richards , C. , Harnish , D. , Lansdorp , P. and Baumann , H.Interferon β2/B‐cell stimulatory factor type 2 shares identity with monocyte‐derived hepatocyte‐stimulating factor and regulates the major acute phase protein response in liver cells . Proc. Natl. Acad. Sci. USA , 84 , 7251 – 7255 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9. ) Michiel , D. F. and Oppenheim , J. J.Cytokines as positive and negative regulators of tumor promotion and progression . Semin. Cancer Biol. , 3 , 3 – 15 ( 1992. ). [PubMed] [Google Scholar]
  • 10. ) Eustace , K. , Han , X. , Gooding , R. , Rowbottom , A. , Riches , P. and Heyderman , E.Interleukin‐6 (IL‐6) functions as an autocrine growth factor in cervical carcinomas in vitro . Gynecol. Oncol. , 50 , 15 – 19 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 11. ) Miki , S. , Iwano , M. , Miki , Y. , Yamamoto , ML , Tang , B. , Yokokawa , K. , Sonoda , T. , Hirano , T. and Kishimoto , T.Interleukin‐6 (IL‐6) functions as an in vitro autocrine growth factor in renal cell carcinomas . FEES Lett. , 250 , 607 – 610 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 12. ) Lahm , H. , Petral‐Malec , D. , Yilmaz‐Ceyhan , A. , Fischer , J. R. , Lorensoni , M. , Givel , J. C. and Odartchenko , N.Growth stimulation of a human colorectal carcinoma cell line by interleukin‐1 and ‐6 and antagonistic effects of transforming growth factor β1 . Eur. J. Cancer , 28A , 1894 – 1899 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 13. ) Oster , W. , Cicco , N. A. , Klein , H. , Hirano , T. , Kishimoto , T. , Lindemann , A. , Mertelsmann , R. H. and Herrmann , F.Participation of the cytokines interleukin 6, tumor necrosis factor‐a and interleukin 1‐β secreted by acute myeloge‐nous leukemia blasts in autocrine and paracrine leukemia growth control . J. Clin. Invest. , 84 , 451 – 457 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
  • 14. ) Kawano , M. , Hirano , T. , Masuda , T. , Taga , T. , Horii , Y. , p15INK4B Iwato , K. , Asaoku , H. , Tang , B. , Tanabe , O. and Tanaka , H.Autocrine generation and essential requirement of BSF‐2/IL‐6 for human multiple myelomas . Nature , 332 , 83 – 85 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 15. ) Ochiai , A. , Yasui , W. and Tahara , E.Growth‐promoting effect of gastrin on human gastric carcinoma cell line TMK‐1 . Jpn. J. Cancer Res. , 76 , 1064 – 1071 ( 1985. ). [PubMed] [Google Scholar]
  • 16. ) Yanagthara , K. , Seyama , T. , Tsumuraya , M. , Kamada , N. and Yokoro , K.Establishment and characterization of human signet ring cell gastric carcinoma cell lines with amplification of the c‐myc oncogene . Cancer Res. , 51 , 381 – 386 ( 1991. ). [PubMed] [Google Scholar]
  • 17. ) Maniatis , T. , Fritsch , E. F. and Sambrock , J.Molecular Cloning. A Laboratory Manual , 2nd Ed. , pp. 719 – 729 ( 1989. ). Cold Spring Harbor Laboratory; , New York . [Google Scholar]
  • 18. ) Yoshida , K. , Kyo , E. , Tsujino , T. , Sano , T. , Niimoto , M. and Tahara , E.Expression of epidermal growth factor, transforming growth factor‐α and their receptor genes in human gastric carcinomas: implication for autocrine growth . Jpn. J. Cancer Res. , 81 , 43 – 51 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19. ) Dinarello , C. A.Biology of interleukin 1 . FASEB J. , 2 , 108 – 115 ( 1988. ). [PubMed] [Google Scholar]
  • 20. ) van Snick , J.Interleukin‐6: an overview . Annu. Rev. Immunol , 8 , 253 – 278 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 21. ) Kishimoto , T. , Akira , S. , Narazaki , M. and Taga , T.Interleukin‐6 family of cytokines and gp130 . Blood , 86 , 1243 – 1254 ( 1995. ). [PubMed] [Google Scholar]
  • 22. ) Hirano , T. , Akira , S. , Taga , T. and Kishimoto , T.Biological and clinical aspects of interleukin 6 . Immunol. Today , 11 , 443 – 449 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 23. ) Poli , V. , Balena , R. , Fattori , E. , Markatos , A. , Yamamoto , M. , Tanaka , H. , Ciliberto , O. , Rodan , G. A. and Costantini , F.Interleukin‐6 deficient mice are protected from bone loss caused by estrogen depletion . EMBO J. , 13 , 1189 – 1196 ( 1994. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24. ) Hilbert , D. M. , Kopf , M. , Mock , B. A. , Koehler , G. and Rodikoff , S.Interleukin 6 is essential for in vivo development of B lineage neoplasm . J. Exp. Med. , 182 , 243 – 248 ( 1995. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25. ) Hirano , T. and Kishimoto , T.Interleukin 6 and plasma cell neoplasia . Prog. Growth Factor Res. , 1 , 133 – 141 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 26. ) Eustace , D. , Han , X. , Gooding , R. , Rowbottom , A. , Riches , P. and Heyderman , E.Interleukin‐6 (IL‐6) functions as an autocrine growth factor in cervical carcinomas in vitro . Gynecol. Oncol. , 50 , 15 – 19 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 27. ) Siegall , C. B. , Schwab , G. , Nordan , R. P. , FitzGerald , D. J. and Pastan , I.Expression of the interleukin 6 receptor and interleukin 6 in prostate carcinoma cells . Cancer Res. , 50 , 7786 – 7788 ( 1990. ). [PubMed] [Google Scholar]
  • 28. ) Okamoto , M. , Lee , C. and Oyasu , R.Interleukin‐6 as a paracrine and autocrine growth factor in human prostatic carcinoma cells in vitro . Cancer Res. , 57 , 141 – 146 ( 1997. ). [PubMed] [Google Scholar]
  • 29. ) Takeda , K. , Fujii , N. , Nitta , Y. , Sakihara , H. , Nakayama , K. , Rikiishi , H. and Kumagai , K.Murine tumor cells metastasizing selectively in the liver: ability to produce hepatocyte‐activating cytokines interleukin‐1 and/or ‐6 . Jpn. J. Cancer Res. , 82 , 1299 – 1308 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30. ) Klein , B. , Wijdenes , J. , Zhang , X.‐G. , Jourdan , M. , Boiron , J.‐M. , Brochier , J. , Liautard , J. , Merlin , M. , Clement , C. , Mourel‐Fournier , B. , Zhao‐Liang , L. , Mannoni , T. , Sany , J. and Bataille , R.Murine anti‐interleukin‐6 monoclonal antibody therapy for a patient with plasma cell leukemia . Blood , 78 , 1198 – 1204 ( 1991. ). [PubMed] [Google Scholar]
  • 31. ) Bataille , R. , Barlogie , B. , Lu , Z. Y. , Rossi , J.‐F. , Lavabre‐Bertrand , T. , Beck , T. , Wijdenes , J. , Brochier , J. and Klein , B.Biologic effects of anti‐interleukin‐6 murine monoclonal antibody in advanced multiple myeloma . Blood , 86 , 685 – 691 ( 1995. ). [PubMed] [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES