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British Journal of Cancer logoLink to British Journal of Cancer
. 2000 Jul 24;83(4):519–525. doi: 10.1054/bjoc.2000.1257

Down-regulation of TGF- β 1 production restores immunogenicity in prostate cancer cells

E Matthews 1, T Yang 1, L Janulis 1, S Goodwin 1, S D Kundu 1, W J Karpus 2, C Lee 1
PMCID: PMC2374659  PMID: 10945501

Abstract

The objective of this study is to determine if a non-immunogenic Dunning’s rat prostate cancer cell line, MATLyLu, can become immunogenic by reducing the endogenous production of TGF-β1. An expression construct containing a DNA sequence in an antisense orientation to TGF-β1 (TGF-β1 antisense) was stably transfected into MATLyLu cells. Following transfection, cellular content of TGF-β1 reduced from 70 to10 pg per 2 × 104cells and the rate of in vitro3H-thymidine incorporation increased 3–5-fold. After subcutaneous injection of tumour cells into syngeneic male hosts (Copenhagen rats), the tumour incidence was 100% (15/15) for the wild type MATLyLu cells and cells transfected with the control construct, but only 43% (9/21, P≤ 0.05) for cells transfected with TGF-β1 antisense. However, when cells were injected into immunodeficient hosts (athymic nude rats), the incidence of tumour development was 100% (10/10) for both the wild type MATLyLu cells and cells transfected with the control construct and 90% (9/10) for cells transfected with TGF-β1 antisense. These observations support the concept that MATLyLu cells are immunogenic, when the endogenous production of TGF-β1 is down-regulated. © 2000 Cancer Research Campaign

Keywords: TGF-β, expression, rat prostate cancer, immunogenicity, tumour incidence, host–tumour interaction

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Selected References

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  1. Barrack E. R. TGF beta in prostate cancer: a growth inhibitor that can enhance tumorigenicity. Prostate. 1997 Apr 1;31(1):61–70. doi: 10.1002/(sici)1097-0045(19970401)31:1<61::aid-pros10>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
  2. Battegay E. J., Raines E. W., Seifert R. A., Bowen-Pope D. F., Ross R. TGF-beta induces bimodal proliferation of connective tissue cells via complex control of an autocrine PDGF loop. Cell. 1990 Nov 2;63(3):515–524. doi: 10.1016/0092-8674(90)90448-n. [DOI] [PubMed] [Google Scholar]
  3. Fakhrai H., Dorigo O., Shawler D. L., Lin H., Mercola D., Black K. L., Royston I., Sobol R. E. Eradication of established intracranial rat gliomas by transforming growth factor beta antisense gene therapy. Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2909–2914. doi: 10.1073/pnas.93.7.2909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gomella L. G., Sargent E. R., Wade T. P., Anglard P., Linehan W. M., Kasid A. Expression of transforming growth factor alpha in normal human adult kidney and enhanced expression of transforming growth factors alpha and beta 1 in renal cell carcinoma. Cancer Res. 1989 Dec 15;49(24 Pt 1):6972–6975. [PubMed] [Google Scholar]
  5. Isaacs J. T., Isaacs W. B., Feitz W. F., Scheres J. Establishment and characterization of seven Dunning rat prostatic cancer cell lines and their use in developing methods for predicting metastatic abilities of prostatic cancers. Prostate. 1986;9(3):261–281. doi: 10.1002/pros.2990090306. [DOI] [PubMed] [Google Scholar]
  6. Isaacs J. T., Yu G. W., Coffey D. S. The characterization of a newly identified, highly metastatic variety of Dunning R 3327 rat prostatic adenocarcinoma system: the MAT LyLu tumor. Invest Urol. 1981 Jul;19(1):20–23. [PubMed] [Google Scholar]
  7. Janik P., Briand P., Hartmann N. R. The effect of estrone-progesterone treatment on cell proliferation kinetics of hormone-dependent GR mouse mammary tumors. Cancer Res. 1975 Dec;35(12):3698–3704. [PubMed] [Google Scholar]
  8. Karpus W. J., Swanborg R. H. CD4+ suppressor cells inhibit the function of effector cells of experimental autoimmune encephalomyelitis through a mechanism involving transforming growth factor-beta. J Immunol. 1991 Feb 15;146(4):1163–1168. [PubMed] [Google Scholar]
  9. Laiho M., DeCaprio J. A., Ludlow J. W., Livingston D. M., Massagué J. Growth inhibition by TGF-beta linked to suppression of retinoblastoma protein phosphorylation. Cell. 1990 Jul 13;62(1):175–185. doi: 10.1016/0092-8674(90)90251-9. [DOI] [PubMed] [Google Scholar]
  10. Letterio J. J., Roberts A. B. Regulation of immune responses by TGF-beta. Annu Rev Immunol. 1998;16:137–161. doi: 10.1146/annurev.immunol.16.1.137. [DOI] [PubMed] [Google Scholar]
  11. Morton D. M., Barrack E. R. Modulation of transforming growth factor beta 1 effects on prostate cancer cell proliferation by growth factors and extracellular matrix. Cancer Res. 1995 Jun 15;55(12):2596–2602. [PubMed] [Google Scholar]
  12. Pietenpol J. A., Holt J. T., Stein R. W., Moses H. L. Transforming growth factor beta 1 suppression of c-myc gene transcription: role in inhibition of keratinocyte proliferation. Proc Natl Acad Sci U S A. 1990 May;87(10):3758–3762. doi: 10.1073/pnas.87.10.3758. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Shaw M. W., Rubenstein M., Dubin A., McKiel C. F., Guinan P. D. Effect of cyclophosphamide on leukocytic subset distributions in rats carrying the Dunning R3327-MAT-LyLu prostatic adenocarcinoma. Prostate. 1987;11(2):117–125. doi: 10.1002/pros.2990110203. [DOI] [PubMed] [Google Scholar]
  14. Sherman L. A., Chattopadhyay S. The molecular basis of allorecognition. Annu Rev Immunol. 1993;11:385–402. doi: 10.1146/annurev.iy.11.040193.002125. [DOI] [PubMed] [Google Scholar]
  15. Smolev J. K., Heston W. D., Scott W. W., Coffey D. S. Characterization of the Dunning R3327H prostatic adenocarcinoma: an appropriate animal model for prostatic cancer. Cancer Treat Rep. 1977 Mar-Apr;61(2):273–287. [PubMed] [Google Scholar]
  16. Steiner M. S., Barrack E. R. Transforming growth factor-beta 1 overproduction in prostate cancer: effects on growth in vivo and in vitro. Mol Endocrinol. 1992 Jan;6(1):15–25. doi: 10.1210/mend.6.1.1738367. [DOI] [PubMed] [Google Scholar]
  17. Vieweg J., Rosenthal F. M., Bannerji R., Heston W. D., Fair W. R., Gansbacher B., Gilboa E. Immunotherapy of prostate cancer in the Dunning rat model: use of cytokine gene modified tumor vaccines. Cancer Res. 1994 Apr 1;54(7):1760–1765. [PubMed] [Google Scholar]
  18. Welch D. R., Fabra A., Nakajima M. Transforming growth factor beta stimulates mammary adenocarcinoma cell invasion and metastatic potential. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7678–7682. doi: 10.1073/pnas.87.19.7678. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Yang E. Y., Moses H. L. Transforming growth factor beta 1-induced changes in cell migration, proliferation, and angiogenesis in the chicken chorioallantoic membrane. J Cell Biol. 1990 Aug;111(2):731–741. doi: 10.1083/jcb.111.2.731. [DOI] [PMC free article] [PubMed] [Google Scholar]

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