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. 1995 Sep;41(5):309–316. doi: 10.1007/BF01517219

Antiproliferative effects of bacillus Calmette-Guérin and interferon α2b on human bladder cancer cells in vitro

Kimberley Pryor 1,✉, Phillip Stricker 2, Pamela Russell 3,4, David Golovsky 2, Ronald Penny 1,4
PMCID: PMC11037707  PMID: 8536277

Abstract

Direct inhibitory effects of bacillus Calmette-Guérin (BCG) and interferon α2b (IFNα2b) on six human bladder carcinoma cell lines, UCRU-BL-13, UCRU-BL-17, UCRU-BL-28, 5637, T24 and J82, were studied using an in vitro proliferation assay. Effects on proliferation following exposure to BCG or IFNα2b were analysed by [3H]thymidine incorporation over 7 days. BCG had an antiproliferative effect on all bladder lines, while sensitivity to IFNα2b varied greatly, being as remarkably low as 1 U/ml for some lines. The antiproliferative effect was greatest when cells were exposed continuously to either agent, but was still evident with a limited exposure. When clinical concentrations were simulated in vitro, BCG+IFNα2b was more effective than BCG alone and as effective as a double BCG concentration. We conclude that, in addition to their immunomodulatory effects, BCG and IFNα2b directly inhibit the proliferation of human bladder cancer cells, and often at extremely low concentrations.

Key words: Bladder neoplasms, Carcinoma transitional cell, BCG vaccine, Interferon, Immunotherapy

References

  • 1.Morales A, Eidinger D, Bruce AW. Intracavitary bacillus Calmette-Guérin in the treatment of superficial bladder tumours. J Urol. 1976;116:180. doi: 10.1016/s0022-5347(17)58737-6. [DOI] [PubMed] [Google Scholar]
  • 2.Lamm DL, Van Der Meijden ADPM, Morales A, Brosman SA, Catalona WJ, Herr HW, Soloway MS, Steg A, Debruyne FMJ. Incidence and treatment of complications of bacillus Calmette-Guérin intravesical therapy in superficial bladder cancer. J Urol. 1992;147:596. doi: 10.1016/s0022-5347(17)37316-0. [DOI] [PubMed] [Google Scholar]
  • 3.Ratliff TL, Gillen D, Catalona WJ. Requirement of a thymus dependent immune response for BCG-mediated antitumour activity. J Urol. 1987;137:155. doi: 10.1016/s0022-5347(17)43909-7. [DOI] [PubMed] [Google Scholar]
  • 4.Bohle A, Thanhauser A, Ulmer AJ, Ernst M, Flad HD, Jocham D. Dissecting the immunobiological effects of bacillus Calmette-Guérin (BCG) in vitro: evidence of a distinct BCG-activated killer (BAK) cell phenomenon. J Urol. 1993;150:1932. doi: 10.1016/s0022-5347(17)35941-4. [DOI] [PubMed] [Google Scholar]
  • 5.Becich MJ, Carroll S, Ratliff TL. Internalization of bacille Calmette-Guérin by bladder tumour cells. J Urol. 1991;145:1316. doi: 10.1016/s0022-5347(17)38622-6. [DOI] [PubMed] [Google Scholar]
  • 6.Akaza H, Iwasaki A, Ohtani M, Ikeda N, Niijima K, Toida I, Koiso K. Expression of antitumor response: role of attachment and viability of bacillus Calmette-Guérin to bladder cancer cells. Cancer. 1993;72:558. doi: 10.1002/1097-0142(19930715)72:2<558::aid-cncr2820720237>3.0.co;2-h. [DOI] [PubMed] [Google Scholar]
  • 7.Kuroda K, Brown EJ, Telle B, Russell DG, Ratliff TL. Characterization of the internalization of bacillus Calmette-Guérin by human bladder tumor cells. J Clin Invest. 1993;91:69. doi: 10.1172/JCI116202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Ratliff TL. BCG immunotherapy in bladder cancer. Padova: Cooperativa Libraria Editrice Universita di Padova; 1994. Mechanism of action of intravesical BCG for superficial bladder cancer; p. 25. [Google Scholar]
  • 9.Torti FM, Shortliffe LD, Williams RD, Pitts WC, Kempson RL, Ross JC, Palmer J, Meyers F, Ferrari M, Hannigan J, Spiegel R, McWhirter K, Freiha F. Alpha-interferon in superficial bladder cancer: a Northern California Oncology Group study. J Clin Oncol. 1988;6:476. doi: 10.1200/JCO.1988.6.3.476. [DOI] [PubMed] [Google Scholar]
  • 10.Borden EC, Groveman DS, Nasu T, Renzikoff C, Bryan GT. Antiproliferative activities of interferons against human bladder carcinoma cell lines in vitro. J Urol. 1984;132:800. doi: 10.1016/s0022-5347(17)49877-6. [DOI] [PubMed] [Google Scholar]
  • 11.Torti FM, Lum BL. Superficial bladder cancer. Risk of recurrence and potential role for interferon therapy. Cancer. 1987;59:613. doi: 10.1002/1097-0142(19870201)59:3+<613::aid-cncr2820591307>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]
  • 12.Sen GC, Lengyel P. Minireview. The interferon system. J Biol Chem. 1992;267:5017. [PubMed] [Google Scholar]
  • 13.Shuai K. Interferon-activated signal transduction to the nucleus. Curr Opin Cell Biol. 1994;6:253. doi: 10.1016/0955-0674(94)90144-9. [DOI] [PubMed] [Google Scholar]
  • 14.Pryor K, Goddard J, Goldstein D, Stricker P, Russell P, Golovsky D, Penny R. Bacillus Calmette-Guérin (BCG) enhances monocyte- and lymphocyte-mediated bladder tumour cell killing. Br J Cancer. 1995;71:801. doi: 10.1038/bjc.1995.155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Russell PJ, Wass J, Lukeis R, Garson OM, Jelbart M, Wills E, Philips J, Brown J, Carrington N, Vincent PC, Raghavan D. Characterization of cell lines derived from a multiply aneuploid human bladder transitional-cell carcinoma, UCRU-BL-13. Int J Cancer. 1989;44:276. doi: 10.1002/ijc.2910440216. [DOI] [PubMed] [Google Scholar]
  • 16.Russell PJ, Jelbart M, Wills E, Singh S, Wass J, Wotherspoon J, Raghavan D. Establishment and characterization of a new human bladder cancer cell line showing features of squamous and glandular differentiation. Int J Cancer. 1988;41:74. doi: 10.1002/ijc.2910410115. [DOI] [PubMed] [Google Scholar]
  • 17.Russell PJ, Palavidis Z, Rozinova E, Philips J, Wills EJ, Lukeis R, Wass J, Raghavan D. Characterization of a new human bladder cancer cell line, UCRU-BL-28. J Urol. 1993;150:1038. doi: 10.1016/s0022-5347(17)35682-3. [DOI] [PubMed] [Google Scholar]
  • 18.Hawkyard SJ, Jackson AM, James K, Prescott S, Smyth JF, Chisholm GH. The inhibitory effects of interferon gamma on the growth of bladder cancer cells. J Urol. 1992;147:1399. doi: 10.1016/s0022-5347(17)37582-1. [DOI] [PubMed] [Google Scholar]
  • 19.Jakse G, Marth C, Zechner J, Daxenbichler G. Antiproliferative effect of Hu-interferon-gamma in 674V and J82 bladder carcinoma cell lines. Urol Res. 1988;16:403. doi: 10.1007/BF00280019. [DOI] [PubMed] [Google Scholar]
  • 20.Grups JW, Bange F-CH. Interferon receptors on the surface of interferon-sensitive and interferon-resistant urothelial carcinomas. Urol Res. 1990;18:119. doi: 10.1007/BF00302471. [DOI] [PubMed] [Google Scholar]
  • 21.Ucer U, Bartsch H, Scheurich P, Pfizenmaier K. Biological effects of γ-interferon on human tumor cells: quantity and affinity of cell membrane receptors for γ-IFN in relation to growth inhibition and induction of HLA-DR expression. Int J Cancer. 1985;36:103. doi: 10.1002/ijc.2910360116. [DOI] [PubMed] [Google Scholar]
  • 22.Prescott S, James K, Hargreave TB, Chisholm GD, Smyth JF. Radio-immunoassay detection of interferon-gamma in urine after intravesical Evans BCG therapy. J Urol. 1990;144:1248. doi: 10.1016/s0022-5347(17)39713-6. [DOI] [PubMed] [Google Scholar]
  • 23.Bubenik J, Baresova M, Viklicky V, Jakoubkova J, Sainerova H, Donner J. Established cell line of urinary bladder carcinoma (T24) containing tumour-specific antigen. Int J Cancer. 1973;11:765. doi: 10.1002/ijc.2910110327. [DOI] [PubMed] [Google Scholar]
  • 24.O'Toole C, Price ZH, Ohnuki Y, Unsgaard B. Ultrastructure, karyology and immunology of a cell line originated from a human transitional-cell carcinoma. Br J Cancer. 1978;38:64. doi: 10.1038/bjc.1978.164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Horoszewicz JS, Leong SS, Carter WA. Noncycling tumor cells are sensitive targets for the antiproliferative activity of human interferon. Science. 1979;206:1091. doi: 10.1126/science.493995. [DOI] [PubMed] [Google Scholar]
  • 26.Jackson AM, Alexandroff AB, Fleming D, Prescott S, Chisholm GD, Carter GD, James K. Bacillus Calmette-Guérin (BCG) organisms directly alter the growth of bladder tumour cells. Int J Oncol. 1994;5:697. doi: 10.3892/ijo.5.3.697. [DOI] [PubMed] [Google Scholar]
  • 27.Jackson AM, James K. Understanding the most successful immunotherapy for cancer. Immunologist. 1994;2:208. [Google Scholar]
  • 28.Patard JJ, Chopin DK, Boccon-Gibod L. Mechanisms of action of bacillus Calmette-Guérin in the treatment of superficial bladder cancer. World J Urol. 1993;11:165. doi: 10.1007/BF00211413. [DOI] [PubMed] [Google Scholar]
  • 29.Grups JW, Frohmuller HGW. Antiproliferative effects of interferons against human bladder carcinoma cell lines in vitro. Urol Int. 1988;43:265. doi: 10.1159/000281351. [DOI] [PubMed] [Google Scholar]

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