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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1986 Dec;83(24):9739–9743. doi: 10.1073/pnas.83.24.9739

Oncostatin M: a growth regulator produced by differentiated histiocytic lymphoma cells.

J M Zarling, M Shoyab, H Marquardt, M B Hanson, M N Lioubin, G J Todaro
PMCID: PMC387216  PMID: 3540948

Abstract

A polypeptide termed oncostatin M, which inhibits the replication of A375 melanoma and other human tumor cells, but not normal human fibroblasts, has been isolated from serum-free supernatants of U-937 histiocytic lymphoma cells that have been induced to differentiate into macrophage-like cells following treatment with the phorbol ester phorbol 12-myristate 13-acetate. No such growth inhibitory activity is detected in the supernatant of untreated U-937 cells, indicating that the protein is induced or increased in expression in the phorbol ester-induced differentiated cells. Oncostatin M is stable between pH 2 and 11 and after heating for 1 hr at 56 degrees C but is not stable at 90 degrees C. Purification of oncostatin M has been achieved by gel chromatography and reversed-phase HPLC, using sequentially acetonitrile and n-propanol in the presence of aqueous trifluoroacetic acid. The apparent molecular weight of oncostatin M is approximately 18,000, as determined by gel chromatography, and 28,000, as determined by polyacrylamide gel electrophoresis. The amino-terminal amino acid sequence of the purified polypeptide has been determined. No substantial sequence homology between oncostatin M and other proteins was found, including other tumor cell inhibitory proteins produced by mononuclear cells. Oncostatin M, therefore, appears to represent a distinct cell growth regulator.

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Selected References

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  1. Alexander P., Evans R. Endotoxin and double stranded RNA render macrophages cytotoxic. Nat New Biol. 1971 Jul 21;232(29):76–78. doi: 10.1038/newbio232076a0. [DOI] [PubMed] [Google Scholar]
  2. Allen G., Fantes K. H. A family of structural genes for human lymphoblastoid (leukocyte-type) interferon. Nature. 1980 Oct 2;287(5781):408–411. doi: 10.1038/287408a0. [DOI] [PubMed] [Google Scholar]
  3. Blyden G., Handschumacher R. E. Purification and properties of human lymphocyte activating factor (LAF). J Immunol. 1977 May;118(5):1631–1638. [PubMed] [Google Scholar]
  4. Carey T. E., Takahashi T., Resnick L. A., Oettgen H. F., Old L. J. Cell surface antigens of human malignant melanoma: mixed hemadsorption assays for humoral immunity to cultured autologous melanoma cells. Proc Natl Acad Sci U S A. 1976 Sep;73(9):3278–3282. doi: 10.1073/pnas.73.9.3278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Carswell E. A., Old L. J., Kassel R. L., Green S., Fiore N., Williamson B. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3666–3670. doi: 10.1073/pnas.72.9.3666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Degliantoni G., Murphy M., Kobayashi M., Francis M. K., Perussia B., Trinchieri G. Natural killer (NK) cell-derived hematopoietic colony-inhibiting activity and NK cytotoxic factor. Relationship with tumor necrosis factor and synergism with immune interferon. J Exp Med. 1985 Nov 1;162(5):1512–1530. doi: 10.1084/jem.162.5.1512. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Derynck R., Jarrett J. A., Chen E. Y., Goeddel D. V. The murine transforming growth factor-beta precursor. J Biol Chem. 1986 Apr 5;261(10):4377–4379. [PubMed] [Google Scholar]
  8. Edman P., Begg G. A protein sequenator. Eur J Biochem. 1967 Mar;1(1):80–91. doi: 10.1007/978-3-662-25813-2_14. [DOI] [PubMed] [Google Scholar]
  9. Fidler I. J. Macrophages and metastasis--a biological approach to cancer therapy. Cancer Res. 1985 Oct;45(10):4714–4726. [PubMed] [Google Scholar]
  10. Fidler I. J., Sone S., Fogler W. E., Barnes Z. L. Eradication of spontaneous metastases and activation of alveolar macrophages by intravenous injection of liposomes containing muramyl dipeptide. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1680–1684. doi: 10.1073/pnas.78.3.1680. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fiers W., Remaut E., Devos R., Cheroutre H., Contreras R., Gheysen D., Degrave W., Stanssens P., Tavernier J., Taya Y. The human fibroblast and human immune interferon genes and their expression in homologous and heterologous cells. Philos Trans R Soc Lond B Biol Sci. 1982 Sep 24;299(1094):29–38. doi: 10.1098/rstb.1982.0103. [DOI] [PubMed] [Google Scholar]
  12. Fryling C. M., Iwata K. K., Johnson P. A., Knott W. B., Todaro G. J. Two distinct tumor cell growth-inhibiting factors from a human rhabdomyosarcoma cell line. Cancer Res. 1985 Jun;45(6):2695–2699. [PubMed] [Google Scholar]
  13. Gately M. K., Mayer M. M., Henney C. S. Effect of anti-lymphotoxin on cell-mediated cytotoxicity. Evidence for two pathways, one involving lymphotoxin and the other requiring intimate contact between the plasma membranes of killer and target cells. Cell Immunol. 1976 Nov;27(1):82–93. doi: 10.1016/0008-8749(76)90156-8. [DOI] [PubMed] [Google Scholar]
  14. Giard D. J., Aaronson S. A., Todaro G. J., Arnstein P., Kersey J. H., Dosik H., Parks W. P. In vitro cultivation of human tumors: establishment of cell lines derived from a series of solid tumors. J Natl Cancer Inst. 1973 Nov;51(5):1417–1423. doi: 10.1093/jnci/51.5.1417. [DOI] [PubMed] [Google Scholar]
  15. Gray P. W., Leung D. W., Pennica D., Yelverton E., Najarian R., Simonsen C. C., Derynck R., Sherwood P. J., Wallace D. M., Berger S. L. Expression of human immune interferon cDNA in E. coli and monkey cells. Nature. 1982 Feb 11;295(5849):503–508. doi: 10.1038/295503a0. [DOI] [PubMed] [Google Scholar]
  16. HAYFLICK L. THE LIMITED IN VITRO LIFETIME OF HUMAN DIPLOID CELL STRAINS. Exp Cell Res. 1965 Mar;37:614–636. doi: 10.1016/0014-4827(65)90211-9. [DOI] [PubMed] [Google Scholar]
  17. Hammerstrøm J. Human monocyte-mediated cytotoxicity to K-562 cells: activation by lymphokines. Scand J Immunol. 1979;10(6):575–584. doi: 10.1111/j.1365-3083.1979.tb01392.x. [DOI] [PubMed] [Google Scholar]
  18. Harris P. E., Ralph P., Litcofsky P., Moore M. A. Distinct activities of interferon-gamma, lymphokine and cytokine differentiation-inducing factors acting on the human monoblastic leukemia cell line U937. Cancer Res. 1985 Jan;45(1):9–13. [PubMed] [Google Scholar]
  19. Hewick R. M., Hunkapiller M. W., Hood L. E., Dreyer W. J. A gas-liquid solid phase peptide and protein sequenator. J Biol Chem. 1981 Aug 10;256(15):7990–7997. [PubMed] [Google Scholar]
  20. Horowitz J. B., Kaye J., Conrad P. J., Katz M. E., Janeway C. A., Jr Autocrine growth inhibition of a cloned line of helper T cells. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1886–1890. doi: 10.1073/pnas.83.6.1886. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hunkapiller M. W., Hood L. E. Protein sequence analysis: automated microsequencing. Science. 1983 Feb 11;219(4585):650–659. doi: 10.1126/science.6687410. [DOI] [PubMed] [Google Scholar]
  22. Hunkapiller M. W., Lujan E., Ostrander F., Hood L. E. Isolation of microgram quantities of proteins from polyacrylamide gels for amino acid sequence analysis. Methods Enzymol. 1983;91:227–236. doi: 10.1016/s0076-6879(83)91019-4. [DOI] [PubMed] [Google Scholar]
  23. Iwata K. K., Fryling C. M., Knott W. B., Todaro G. J. Isolation of tumor cell growth-inhibiting factors from a human rhabdomyosarcoma cell line. Cancer Res. 1985 Jun;45(6):2689–2694. [PubMed] [Google Scholar]
  24. Knudsen P. J., Dinarello C. A., Strom T. B. Purification and characterization of a unique human interleukin 1 from the tumor cell line U937. J Immunol. 1986 May 1;136(9):3311–3316. [PubMed] [Google Scholar]
  25. Lachman L. B., Dinarello C. A., Llansa N. D., Fidler I. J. Natural and recombinant human interleukin 1-beta is cytotoxic for human melanoma cells. J Immunol. 1986 Apr 15;136(8):3098–3102. [PubMed] [Google Scholar]
  26. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  27. Levy W. P., Shively J., Rubinstein M., Del Valle U., Pestka S. Amino-terminal amino acid sequence of human leukocyte interferon. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5102–5104. doi: 10.1073/pnas.77.9.5102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Mantovani A., Jerrells T. R., Dean J. H., Herberman R. B. Cytolytic and cytostatic activity on tumor cells of circulating human monocytes. Int J Cancer. 1979 Jan 15;23(1):18–27. doi: 10.1002/ijc.2910230105. [DOI] [PubMed] [Google Scholar]
  29. March C. J., Mosley B., Larsen A., Cerretti D. P., Braedt G., Price V., Gillis S., Henney C. S., Kronheim S. R., Grabstein K. Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs. Nature. 1985 Jun 20;315(6021):641–647. doi: 10.1038/315641a0. [DOI] [PubMed] [Google Scholar]
  30. Onozaki K., Matsushima K., Aggarwal B. B., Oppenheim J. J. Human interleukin 1 is a cytocidal factor for several tumor cell lines. J Immunol. 1985 Dec;135(6):3962–3968. [PubMed] [Google Scholar]
  31. Pennica D., Nedwin G. E., Hayflick J. S., Seeburg P. H., Derynck R., Palladino M. A., Kohr W. J., Aggarwal B. B., Goeddel D. V. Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature. 1984 Dec 20;312(5996):724–729. doi: 10.1038/312724a0. [DOI] [PubMed] [Google Scholar]
  32. Ransom J. H., Evans C. H., McCabe R. P., Pomato N., Heinbaugh J. A., Chin M., Hanna M. G., Jr Leukoregulin, a direct-acting anticancer immunological hormone that is distinct from lymphotoxin and interferon. Cancer Res. 1985 Feb;45(2):851–862. [PubMed] [Google Scholar]
  33. Rimsky L., Wakasugi H., Ferrara P., Robin P., Capdevielle J., Tursz T., Fradelizi D., Bertoglio J. Purification to homogeneity and NH2-terminal amino acid sequence of a novel interleukin 1 species derived from a human B cell line. J Immunol. 1986 May 1;136(9):3304–3310. [PubMed] [Google Scholar]
  34. Roberts A. B., Anzano M. A., Wakefield L. M., Roche N. S., Stern D. F., Sporn M. B. Type beta transforming growth factor: a bifunctional regulator of cellular growth. Proc Natl Acad Sci U S A. 1985 Jan;82(1):119–123. doi: 10.1073/pnas.82.1.119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Rosenberg S. Lymphokine-activated killer cells: a new approach to immunotherapy of cancer. J Natl Cancer Inst. 1985 Oct;75(4):595–603. [PubMed] [Google Scholar]
  36. Sone S., Mutsuura S., Ishii K., Shirahama T., Tsubura E. In vitro cytotoxicity to various human tumor cell lines of a tumor cytotoxic factor(s) produced by human alveolar macrophages. Gan. 1984 Oct;75(10):920–928. [PubMed] [Google Scholar]
  37. Sugarman B. J., Aggarwal B. B., Hass P. E., Figari I. S., Palladino M. A., Jr, Shepard H. M. Recombinant human tumor necrosis factor-alpha: effects on proliferation of normal and transformed cells in vitro. Science. 1985 Nov 22;230(4728):943–945. doi: 10.1126/science.3933111. [DOI] [PubMed] [Google Scholar]
  38. Sundström C., Nilsson K. Establishment and characterization of a human histiocytic lymphoma cell line (U-937). Int J Cancer. 1976 May 15;17(5):565–577. doi: 10.1002/ijc.2910170504. [DOI] [PubMed] [Google Scholar]
  39. Taniguchi T., Mantei N., Schwarzstein M., Nagata S., Muramatsu M., Weissmann C. Human leukocyte and fibroblast interferons are structurally related. Nature. 1980 Jun 19;285(5766):547–549. doi: 10.1038/285547a0. [DOI] [PubMed] [Google Scholar]
  40. Weissenbach J., Chernajovsky Y., Zeevi M., Shulman L., Soreq H., Nir U., Wallach D., Perricaudet M., Tiollais P., Revel M. Two interferon mRNAs in human fibroblasts: in vitro translation and Escherichia coli cloning studies. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7152–7156. doi: 10.1073/pnas.77.12.7152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Wilbur W. J., Lipman D. J. Rapid similarity searches of nucleic acid and protein data banks. Proc Natl Acad Sci U S A. 1983 Feb;80(3):726–730. doi: 10.1073/pnas.80.3.726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Zoon K. C., Smith M. E., Bridgen P. J., Anfinsen C. B., Hunkapiller M. W., Hood L. E. Amino terminal sequence of the major component of human lymphoblastoid interferon. Science. 1980 Feb 1;207(4430):527–528. doi: 10.1126/science.7352260. [DOI] [PubMed] [Google Scholar]

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