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Methylcholanthrene-induced murine fibrosarcoma cell line BMT-11 secretes granulocyte colony-stimulating factor

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Research in Experimental Medicine

Summary

Murine fibrosarcoma cell line BMT-11 was induced with 3-methyl-cholanthrene and maintained in culture. Transplantation of BMT-11 into syngeneic C57 BL/6 mice produced leukocytosis consisting of marked increments of neutrophils and monocytes associated with massive splenomegaly. In order to elucidate the mechanisms of this leukemoid reaction, we studied the changes occurring in hematopoietic progenitor cells in BMT-11-transplanted mice. The numbers of granulocyte-macrophage colony-forming units (CFU-GM), erythroid colony-forming units (CFU-E), erythroid burst-forming units (BFU-E), and mixed colony-forming units (CFU-Mix) in the spleen showed dramatic 216-fold, 18-fold, 64-fold, and 80-fold increases, respectively, relative to the value in the control mice 5 weeks after the BMT-11 implantation. In contrast, the levels of progenitor cells in the bone marrow remained within normal limits. The nature of the colony-stimulating factor (CSF) secreted from BMT-11 tumor cells was also studied. BMT-11-conditioned medium (BMT-11-CM), BMT-11 tumor extract, and sera from the mice bearing transplanted BMT-11 tumor contained CSF that stimulated mainly granulocyte and macrophage lineages. Furthermore, the expression of the granulocyte colony-stimulating factor (G-CSF) gene in BMT-11 cells were detected by Northern blot analysis.

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References

  1. Ando K, Hunter N, Peters LJ (1979) Immunologically nonspecific enhancement of artificial lung metastases in tumor-bearing mice. Cancer Immunol Immunother 6:151–156

    Article  Google Scholar 

  2. Bateman JC (1951) Leukemoid reactions to transplanted mouse tumors. J Natl Cancer Inst 11:671–688

    PubMed  CAS  Google Scholar 

  3. Bessho M, Hirashima K, Ando K, Nara N, Momoi H (1984) Hemopoietic stem cell kinetics in mice bearing CSF-producing fibrosarcoma. Nippon Ketsueki Gakkai Zasshi 47:21–33

    PubMed  CAS  Google Scholar 

  4. Boggs DR, Mallory E, Boggs SS, Chervenick PA, Lee RE (1977) Kinetic studies of a tumor-induced leukemoid reaction in mice. J Lab Clin Med 89:80–92

    PubMed  CAS  Google Scholar 

  5. Burgess AW, Camakaris J, Metcalf D (1977) Purification of colony-stimulating factor from mouse lung-conditioned medium. J Biol Chem 252:1998–2003

    PubMed  CAS  Google Scholar 

  6. Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ (1979) Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 18:5294–5299

    Article  PubMed  CAS  Google Scholar 

  7. Delmonte L, Liebelt AG, Liebelt RA (1966) Granulopoiesis and thrombopoiesis in mice bearing transplanted mammary cancer. Cancer Res 26:149–159

    PubMed  CAS  Google Scholar 

  8. Glisin V, Crkvenjakov R, Byus C (1974) Ribonucleic acid isolated by cesium chloride centrifugation. Biochemistry 13:2633–2637

    Article  PubMed  CAS  Google Scholar 

  9. Gough NM, Gough J, Metcalf D, Kelso A, Grail D, Nicola NA, Burgess AW, Dunn AR (1984) Molecular cloning of cDNA encoding a murine haematopoietic growth regulator, granulocyte-macrophage colony-stimulating factor. Nature 309:763–767

    Article  PubMed  CAS  Google Scholar 

  10. Hara H, Ogawa M (1978) Murine hemopoietic colonies in culture containing normoblasts, macrophages, and megakaryocytes. Am J Hematol 4:23–34

    Article  PubMed  CAS  Google Scholar 

  11. Hayashi S, Okamura S, Asano Y, Ohhara N, Otsuka T, Shibuya T, Otsuka T, Niho Y (1987) Human bladder carcinoma cell line HTB9, which secretes a factor to stimulate clonogenic leukemic blast growth, expresses the granulocyte-macrophage colony-stimulating factor gene. Jpn J Cancer Res 78:1224–1228

    PubMed  CAS  Google Scholar 

  12. Ihle JN, Keller J, Oroszlan S, Henderson LE, Copeland TD, Fitch F, Prystowsky MB, Goldwasser E, Schrader JW, Paraszynski E, Dy M, Label B (1983) Biologic properties of homogeneous interleukin 3. J Immunol 131:282–287

    PubMed  CAS  Google Scholar 

  13. Ikebuchi K, Clark SC, Ihle JN, Souza LM, Ogawa M (1988) Granulocyte colony-stimulating factor enhances interleukin 3-dependent proliferation of multipotential hemopoietic progenitors. Proc Natl Acad Sci USA 85:3445–3449

    Article  PubMed  CAS  Google Scholar 

  14. Iscove NN, Sieber F (1975) Erythroid progenitors in mouse bone marrow detected by macroscopic colony formation in culture. Exp Hematol 3:32–43

    PubMed  CAS  Google Scholar 

  15. Iscove NN, Sieber F, Winterhalter KH (1974) Erythroid colony formation in cultures of mouse and human bone marrow: analysis of the requirement for erythropoietin by gel filtration and affinity chromatography on agarose-concanavalin A. J Cell Physiol 83:309–320

    Article  PubMed  CAS  Google Scholar 

  16. Ishikawa M, Hosokawa M, Ohhara N, Niho Y, Kobayashi H (1987) Marked granulocytosis in C57/BL/6 mice bearing a transplanted BMT-11 fibrosarcoma. J Natl Cancer Inst 78:567–571

    PubMed  CAS  Google Scholar 

  17. Johnson GR, Whitehead R, Nicola NA (1985) Effects of a murine mammary tumor on in vivo and in vitro hemopoiesis. Int J Cell Cloning 3:91–105

    Article  PubMed  CAS  Google Scholar 

  18. Kodama T, Sendo F, Kobayashi H (1974) Leukemoid reaction in Balb/c mice bearing transplanted tumors. Cancer Res 34:176–184

    PubMed  CAS  Google Scholar 

  19. Metcalf D, McDonald HR, Odarchenko N, Sordat B (1975) Growth of mouse megakaryocyte colonies in vitro. Proc Natl Acad Sci USA 72:1744–1748

    Article  PubMed  CAS  Google Scholar 

  20. Milas L, Basic I (1972) Stimulated granulocytopoiesis in mice bearing fibrosarcoma. Eur J Cancer Clin Oncol 8:309–313

    CAS  Google Scholar 

  21. Nicola NA, Metcalf D, Matsumoto M, Johnson GR (1983) Purification of a factor inducing differentiation in murine myelomonocytic leukemia cells: identification as granulocyte colony-stimulating factor (G-CSF). J Biol Chem 258:9017–9023

    PubMed  CAS  Google Scholar 

  22. Niho Y, Till JE, McCulloch EA (1975) Granulopoietic progenitors in suspension culture: a comparison of stimulatory cells and conditioned media. Blood 45:811–821

    PubMed  CAS  Google Scholar 

  23. Ohhara N, Okamura S, Niho Y, Otsuka T (1985) Stimulatory effect of an aminopeptidase inhibitor on human bone marrow CFU-C mediated by the interaction of T-lymphocytes. Nippon Ketsueki Gakkai Zasshi 48:134–138

    Google Scholar 

  24. Ohhara N, Okamura S, Otsuka T, Harada M, Niho Y (1987) Stimulatory effect of for-phenicinol on normal human bone marrow granulocyte-macrophage progenitor cells mediated by T-lymphocytes. Biomed Pharmacother 41:425–428

    PubMed  CAS  Google Scholar 

  25. Okamura S, Hayashi S, Asano Y, Shibuya T, Otsuka T, Niho Y (1988) Expression of granulocyte/macrophage colony-stimulating factor gene in leukemic blast cells from patients with acute non-lymphocytic leukemia. Biomed Pharmacother 42:65–68

    PubMed  CAS  Google Scholar 

  26. Reincke U, Burlington H, Carsten AL, Cronkite EP, Laissue JA (1978) Hemopoietic effects in mice of a transplanted granulocytosis-inducing tumor. Exp Hematol 6:421–430

    PubMed  CAS  Google Scholar 

  27. Shimamura M, Kobayashi Y, Yuo A, Urabe A, Okabe T, Komatsu Y, Itoh S, Takaku F (1987) Effect of human recombinant granulocyte colony-stimulating factor on hematopoietic injury in mice induced by 5-fluorouracil. Blood 69:353–355

    PubMed  CAS  Google Scholar 

  28. Stanley RE, heard PM (1977) Factors regulating macrophage production and growth. J Biol Chem 252:4305–4312

    PubMed  CAS  Google Scholar 

  29. Tamura M, Hattori K, Nomura H, Oheda M, Kubota N, Imazeki I, Ono M, Ueyama Y, Nagata S, Shirafuji N, Asano S (1987) Induction of neutrophic granulocytosis in mice by administration of purified human native granulocyte colony-stimulating factor (G-CSF). Biochem Biophys Res Commun 142:454–460

    Article  PubMed  CAS  Google Scholar 

  30. Thomas PS (1980) Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci USA 77:5201–5205

    Article  PubMed  CAS  Google Scholar 

  31. Tsuchiya M, Asano S, Kaziro Y, Nagata S (1987) Isolation and characterization of the cDNA for murine granulocyte colony-stimulating factor. Proc Natl Acad Sci USA 83:7633–7637

    Article  Google Scholar 

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Ohhara, N., Okamura, S., Hayashi, S. et al. Methylcholanthrene-induced murine fibrosarcoma cell line BMT-11 secretes granulocyte colony-stimulating factor. Res. Exp. Med. 190, 305–314 (1990). https://doi.org/10.1007/BF00000037

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  • DOI: https://doi.org/10.1007/BF00000037

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