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Direct and indirect effects of recombinant human granulocyte-colony stimulating factor on in vitro colony formation of human bladder cancer cells

  • Original Articles
  • rG-CSF, Human Bladder Cancer Cells, In Vitro, Proliferating Activity
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Abstract

Although the present experimental use of recombinant human granulocyte-colony-stimulating factor (rG-CSF) has been proven to alleviate the myelosuppression induced by antitumor chemotherapy, it is also believed to stimulate growth of some nonhematopoietic tumor cells. We investigated both the direct and indirect effects of rG-CSF on in vitro colony formation of human bladder cancer cell lines using a modified human tumor clonogenic assay. Peripheral blood mononuclear cells (PBMC) were used as feeder cells (a mixture of 5×104 monocytes/dish and 5×105 lymphocytes/dish obtained from healthy donors). Human bladder cancer cell lines KK-47, TCCSUP and T24, all derived from human transitional-cell carcinomas, were incubated continuously with various concentrations of rG-CSF ranging from 0.01 ng/ml to 10 ng/ml both with and without PBMC for 7–21 days. The concentrations of rG-CSF used were chosen as being in the range of achievable serum concentrations in patients treated with rG-CSF. At the end of incubation, colonies were counted under an inverted phase-contrast microscope, and an increase in the number of colonies in comparison with the control was used to evaluate the effects of rG-CSF. Results were expressed as a percentage of controls. rG-CSF in the upper layer at concentrations ranging from 0.1 ng/ml to 10 ng/ml stimulated the colony formation of all the cancer cell lines tested in the absence of PBMC in the feeder layer, whereas cells with PBMC in the feeder layer were significantly stimulated more than those without PBMC in the feeder layer (P<0.05) up to a certain concentration, which varied from cell line to cell line. At higher concentrations of rG-CSF, no further stimulation but, on the contrary, a decrease in colony formation was observed in cells with PBMC in the feeder layer in all the cell lines tested. Colony formation in KK-47 and T24 cell lines was significantly inhibited at 5 ng/ml and/or 10 ng/ml rG-CSF compared with cells without PBMC in the feeder layer. Our results suggest that rG-CSF may have both direct and indirect stimulatory effects on the growth of human bladder cancer cell lines in vitro. The results obtained also raise the possibility of adverse effects of rG-CSF in bladder cancer patients whose malignant cells may be directly and indirectly stimulated by this factor while it is being used clinically to alleviate the myelosuppression induced by antitumor chemotherapy.

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References

  1. Anon (1989) Focus on summer products. Nature 340: 409

  2. Avalos BR, Gasson JC, Hedvat C, Quan SG, Baldwin GC, Weisbart RH, Williams RE, Golde DW, DiPersio JF (1990) Human granulocyte-colony stimulating factor; biologic activities and receptor characterization on hematopoietic cells and small cell lung cancer cell lines. Blood 75: 851

    PubMed  Google Scholar 

  3. Berdel WE, Danhauser-Riedl S, Steinhauser G, Winton EF (1989) Various human hematopoietic growth factors (interleukin-3, GM-CSF, G-CSF) stimulate clonal growth of nonhematopoietic tumor cells. Blood 73: 80

    PubMed  Google Scholar 

  4. Bubenik J, Baresova M, Viklicky V, Jakoubkova J, Sainerova H, Donner J (1973) Establised cell line of urinary bladder carcinoma (T 24) containing tumor specific antigen. Int J Cancer 11: 765

    PubMed  Google Scholar 

  5. Clark SC, Kamen R (1987) The human hematopoietic colonystimulating factors. Science 236: 1229

    PubMed  Google Scholar 

  6. Chen TR (1977) In situ detection ofMycoplasma contamination in cell cultures by fluorescent Hoechst 33258 stain. Exp Cell Res 104: 255

    PubMed  Google Scholar 

  7. Dinarello CA, Mier JW (1987) Lymphokines. N Engl J Med 317: 940

    PubMed  Google Scholar 

  8. Glenn KC, Ross R (1981) Human monocyte derived growth factor(s) for mesenchymal cells: Activation of secretion by endotoxin and concanavalin A. Cell 25: 603

    PubMed  Google Scholar 

  9. Hamburger AW, Salmon SE (1977) Primary bioassay of human tumor stem cells. Science 197: 461

    PubMed  Google Scholar 

  10. Hamburger AW, Christine PW, Lurie K, Kaplan R (1986) Monocyte derived growth factors for human tumor clonogenic cells. J Leuk Biol 40: 381

    Google Scholar 

  11. Hawkyard SJ, Jackson AM, Prescott S, James K, Chisholm GD (1993) The effect of recombinant cytokines on bladder cancer cells in vitro. J Urol 150: 514

    PubMed  Google Scholar 

  12. Joraschkewitz M, Depenbrock H, Freund M, Erdmann G, Meyer HJ, DeRiese W, Neukam D, Hanauske U, Krumwieh M, Poliwoda H, Hanauske AR (1990) Effects of cytokines on in vitro colony formation of primary human tumour specimens. Eur J Cancer 26: 1070

    PubMed  Google Scholar 

  13. Kaushansky K, Lin N, Adamson JW (1988) Interleukin-1 stimulates fibroblasts to synthesize granulocyte-macrophage and granulocyte colony-stimulating factors. Mechanism for the hematopoietic response to inflammation. J Clin Invest 81: 92

    PubMed  Google Scholar 

  14. Lilly MB, Devlin PE, Devlin JJ, Rado TA (1987) Production of granulocyte colony-stimulating factor by a human melanoma cell line. Exp Hematol 15: 966

    PubMed  Google Scholar 

  15. Levine EG, Raghavan D (1993) MVAC for bladder cancer: time to move forward again (editorial). J Clin Oncol 11: 387

    PubMed  Google Scholar 

  16. Loehrer PJ, Elson P, Dreicer R, Williams R, Hahn R, Nichols CR, Einhorn LH (1992) A phase I–II study: escalated dosages of methotrexate (M), vinblastine (V), doxorubicin (A), and cisplatin (C) plus rhG-CSF in advanced urothelial carcinoma: an ECOG trial (abstract). Proc Am Soc Clin Oncol 11: 201

    Google Scholar 

  17. Nagata S, Tsuchiya M, Asano S, Kaziro Y, Yamazaki T, Yamamoto O, Hirata Y, Kubota N, Oheda M, Nomura H, Ono M (1986) Molecular cloning and expression of cDNA for human granulocyte-colony stimulating factor. Nature 319: 415

    PubMed  Google Scholar 

  18. Nayak SK, O Toole C, Price ZH (1977) A cell line from an anaplastic transitional cell carcinoma of human urinary bladder. Br J Cancer 35: 142

    PubMed  Google Scholar 

  19. Nicola NA, Vades MA, Lopez AF (1986) Down-modulation of receptors for granulocyte activating agents. J Cell Physiol 128: 501

    PubMed  Google Scholar 

  20. Ohigashi T, Tachibana M, Tazaki H, Nakamura K (1992) Bladder cancer cells express functional receptors for granulocyte-colony stimulating factor. J Urol 147: 283

    PubMed  Google Scholar 

  21. Oster W, Lindeman A, Mertelsmann R, Herrmann F (1989) Granulocyte-macrophage colony stimulating factor (CSF) and multilineage CSF recruit human monocytes to express granulocyte CSF. Blood 73: 64

    PubMed  Google Scholar 

  22. Robinson LB, Wichelhausen RH, Roizman B (1956) Contamination of human cell cultures by pleuropneumonia like organisms. Science 124: 1147

    PubMed  Google Scholar 

  23. Sandru G, Veraguth P, Stadler BM (1988) Stimulation of tumor cell growth in humans by a mononuclear cell derived factor. Cancer Res 48: 5411

    PubMed  Google Scholar 

  24. Scher HI, Seidman AD, Bajorin DF, Motzer RJ, Curley T, O'Dell M, Quinlivan S, Fair W, Herr H, Sheinfeld J, Sogani P, Russo P, Dershaw DD, Tao Y, Begg C, Bosl GJ (1992) Escalated methotrexate, vinblastine, adriamycin and cisplatin (E-MAC) with granulocyte colony stimulating factor (G-CSF) in urothelial cancer (abstract). Proc Am Soc Clin Oncol 11: 199

    Google Scholar 

  25. Segawa K, Ueno Y, Kataoka T (1991) In vivo tumor growth enhancement by granulocyte colony-stimulating factor. Jpn J Cancer Res 82: 440

    PubMed  Google Scholar 

  26. Seidman AD, Scher HI, Gabrilove JL, Bajorin DF, Motzer RJ, O'Dell M, Curley T, Dershaw DD, Quinlivan S, Tao Y, Fair WR, Begg C, Bosl GJ (1993) Dose intensification of M-VAC with recombinant granulocyte colony-stimulating factor as initial therapy in advanced urothelial cancer. J Clin Oncol 11: 408

    PubMed  Google Scholar 

  27. Sekiya H, Moriya K, Kanno T (1989) Phase I study of recombinant human G-CSE. Medical Consultation and New Remedies 26: 1660

    Google Scholar 

  28. Sternberg CN, Yagoda A, Scher HI, Watson RC, Ahmed T, Weiselberg LR, Geller N, Hollander PS, Herr HW, Sogani PC, Morse MJ, Whitmore WF (1985) Preliminary results of M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for transitional cell carcinoma of the urothelium. J Urol 133: 403

    PubMed  Google Scholar 

  29. Taya T, Kobayashi T, Tsukahara K, Uchibayashi T, Naito K, Hisazumi H, Kuroda K (1977) In vitro culture of malignant tumor tissue from the human urinary tract. Jpn J Urol 68: 1003

    Google Scholar 

  30. Vallenga E, Rambaldi A, Ernst TJ, Ostapovicz D, Griffin JD (1988) Independent regulation of M-CSF and G-CSF gene expression in human monocytes. Blood 71: 1529

    PubMed  Google Scholar 

  31. Wieser M, Bonifer R, Oster W, Lindemann A, Mertelsmann R, Herrmann F (1989) Interleukin-4 induces secretion of CSF for granulocytes and CSF for mocrophages by peripheral blood monocytes. Blood 73: 1105

    PubMed  Google Scholar 

  32. Wu MC, Cini JK, Yunis AA (1979) Purification of a colonystimulating factor from cultured pancreatic carcinoma cells. J Biol Chem 254: 6226

    PubMed  Google Scholar 

  33. Yamato K, El-Hajjaoui Z, Kuo JF, Koeffler HP (1989) Granulocyte-macrophage colony-stimulating factor: signals for its mRNA accumulation. Blood 74: 1314

    PubMed  Google Scholar 

  34. Zsebo KM, Yuschenkoff VN, Schiffer S, Chang D, McCall E, Dinarello CA, Brown MA, Altrock, Baghy GC, Jr. (1988) Vascular endothelial cells and granulopoiesis interleukin-1 stimulates release of G-CSF and GM-CSF. Blood 71: 99

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Urology, Yamaguchi University School of Medicine, 1144 Kogushi, 755, Ube Yamaguchi, Japan

    Isteaq Ahmed Shameem, Hiroaki Kurisu, Hideyasu Matsuyama, Tomoyuki Shimabukuro & Katsusuke Naito

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  1. Isteaq Ahmed Shameem
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  2. Hiroaki Kurisu
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  3. Hideyasu Matsuyama
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  4. Tomoyuki Shimabukuro
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  5. Katsusuke Naito
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Shameem, I.A., Kurisu, H., Matsuyama, H. et al. Direct and indirect effects of recombinant human granulocyte-colony stimulating factor on in vitro colony formation of human bladder cancer cells. Cancer Immunol Immunother 38, 353–357 (1994). https://doi.org/10.1007/BF01517203

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  • DOI: https://doi.org/10.1007/BF01517203

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