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The Potential Influence of Radiation-Induced Microenvironments in Neoplastic Progression

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Abstract

Ionizing radiation is a complete carcinogen,able both to initiate and promote neoplastic progressionand is a known carcinogen of human and murine mammarygland. Tissue response to radiation is a composite of genetic damage, cell death and induction ofnew gene expression patterns. Although DNA damage isbelieved to initiate carcinogenesis, the contribution ofthese other aspects of radiation response are beginning to be explored. Our studiesdemonstrate that radiation elicits rapid and persistentglobal alterations in the mammary glandmicroenvironment. We postulate that radiation-inducedmicroenvironments may affect epithelial cells neoplastictransformation by altering their number orsusceptibility. Alternatively, radiation inducedmicroenvironments may exert a selective force oninitiated cells and/or be conducive to progression. A key impetus forthese studies is the possibility that blocking theseevents could be a strategy to interrupt neoplasticprogression.

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References

  1. M. J. Bissell and M. H. Barcellos-Hoff (1987). The influence of extracellular matrix on gene expression: Is structure the message? J. Cell Sci. 8: 327-343.

    Google Scholar 

  2. J. J. Decosse, C. L. Gossens, J. F. Kuzma, and D. Unsworth (1973). Breast cancer: Induction of differentiation by embryonic tissue. Science 181: 1057-1058.

    Google Scholar 

  3. M. Cooper and H. Pinkus (1977). Intrauterine transplantation of rat basal cell carcinoma as a model for reconversion of malignant to benign growth. Cancer Res. 37: 2544-2552.

    Google Scholar 

  4. K. Kamiya, J. Yasukawa-Barnes, J. M. Mitchen, M. N. Gould, and K. H. Clifton (1995). Evidence that carcinogenesis involves an imbalance between epigenetic high-frequency initiation and suppression of promotion. Proc. Natl. Acad. Sci. U.S.A. 92: 1332-1336.

    Google Scholar 

  5. E. Farber (1984). Pre-cancerous steps in carcinogenesis. Their physiological adaptive nature. Biochem. Biophys. Acta 738: 171-180.

    Google Scholar 

  6. H. Rubin (1985). Cancer as a dynamic developmental disorder. Cancer Res. 45: 2935-2942.

    Google Scholar 

  7. M. H. Sieweke and M. J. Bissell (1994). The tumor promoting effect of wounding: A possible role for TGFβ induced fibrotic stroma. Crit. Rev. Oncogenesis 5(2/3): 297-311.

    Google Scholar 

  8. M. H. Barcellos-Hoff, J. Aggeler, T. G. Ram, and M. J. Bissell (1989). Functional differentiation and alveolar morphogenesis of primary mammary epithelial cells cultures on reconstituted basement membrane. Development 105: 223-235.

    Google Scholar 

  9. K. L. Schmeichel, V.M. Weaver, M. J. Bissell (1998). Structural cups from the tissue microenvironment are essential determinants of the human mammary epithelial cell phenotype J. Mam. Gland Biol. Neoplasia 3: xx-xx.

    Google Scholar 

  10. G. Bauer (1996). Elimination of transformed cells by normal cells: a novel concept for the control of carcinogenesis Histol. Histopathol. 11(1): 237-255.

    Google Scholar 

  11. H. Fujii, G. R. Cunha, and J. T. Norman (1982). The induction of adenocarinomatous differentiation in neoplastic bladder epithelium by an embryonic prostatic inducer. J. Urology 128: 858-861.

    Google Scholar 

  12. B. E. Elliott, L. Maxwell, M. Arnold, W. Z. Wei, and F. R. Miller (1988). Expression of epithelial-like markers and class I major histocompatibility antigens by a murine carcinoma growing in the mammary gland and in metastases: Orthotopic site effects. Cancer Res. 48: 7237-7245.

    Google Scholar 

  13. T. Sakakura, Y. Sakagami, and Y. Nishizuka (1979). Acceleration of mammary cancer development by grafting of fetal mammary mesenchymes in C3H mice. Gann 70: 459-466.

    Google Scholar 

  14. T. Sakakura, Y. Sakagami, and Y. Nishizuka (1981). Accelerated mammary cancer development by fetal salivary mesenchyme isografted to adult mouse mammary epithelium. JNCI 66: 953-959.

    Google Scholar 

  15. K. B. DeOme, M. J. Miyamoto, R. C. Osborn, R. C. Guzman, and K. Lum (1978). Detection of inapparent nodule transformed cells in the mammary gland tissues of virgin female BALB/cfC3H mice. Cancer Res. 38: 2103-2111.

    Google Scholar 

  16. S. P. Ethier and R. L. Ullrich (1984). Factors influencing expression of mammary ductal dysplasia in cell dissoication-derived murine mammary outgrowths. Cancer Res. 44: 4523-4527.

    Google Scholar 

  17. A. van den Hoof, (1988). Stromal involvement in malignant growth. Adv. Cancer. Res. 50: 159-196.

    Google Scholar 

  18. M. H. Sieweke, N. L. Thompson, M. B. Sporn, and M. J. Bissell (1990). Mediation of wound-related Rous sarcoma virus tumorigenesis and TGF-β. Science 248: 1656-1660.

    Google Scholar 

  19. S. L. Schor, A. M. Schor, P. Durning, and G. Rushton (1985). Skin fibroblasts obtained from cancer patients display foetallike migratory behavior on collagen gels. J. Cell Sci. 73: 235-244.

    Google Scholar 

  20. J. A. Haggie, S. L. Schor, A. Howell, J. M. Birch, and R. A. S. Sellwood (1987). Fibroblasts from relatives of hereditary breast cancer patients display fetal-like behavior in vitro. Lancet 1: 1455-1457.

    Google Scholar 

  21. L. Kopelovich, L. M. Pfeffer, and N. Bias (1979). Growth characteristics of human skin fibroblasts in vitro: A simple experimental approach for the identification of hereditary adenomatosis of the colon and rectum. Cancer 43: 218-223.

    Google Scholar 

  22. S. Rasheed and M. B. Gardner (1981). Growth properties and susceptibility to viral transformation of skin fibroblasts from individuals at high genetic risk for colorectal cancer. JNCI 66: 43-49.

    Google Scholar 

  23. G. M. Hodges, R. M. Hicks, and G. D. Spacey (1977). Epithelial-stromal interactions in normal and chemical carcinogen-treated adult bladder. Cancer Res. 37: 3720-3730.

    Google Scholar 

  24. M. Martin, J. Remy, and F. Daburon (1986). In vitro growth potential of fibroblasts isolated from pigs with radiation-induced fibrosis. Int. J. Rad. Biol. 49: 821-828.

    Google Scholar 

  25. R. G. Panizzoni, W. R. Hanson, D. E. Schwartz, and F. D. Malkinson (1988). Ionizing radiation induces early, sustained increases in collagen biosynthesis: A 48-week study of mouse skin and skin fibroblast cultures. Rad. Res. 116: 145-156.

    Google Scholar 

  26. G. T. Bowden, D. Jaffe, and K. Andrews (1990). Biological and molecular aspects of radiation carcinogenesis in mouse skin. Rad. Res. 121: 235-241.

    Google Scholar 

  27. L. A. Liotta, C. N. Rao, and S. H. Barsky (1983). Tumor invasion and the extracellular matrix. Lab. Invest. 49: 636-649.

    Google Scholar 

  28. M. H. Barcellos-Hoff (1993). Radiation-induced transforming growth factor β and subsequent extracellular matrix reorganization in murine mammary gland. Cancer Res. 53: 3880-3886.

    Google Scholar 

  29. D. P. Penney and W. A. Rosenkrans, Jr. (1984). Cell-cell matrix interactions in induced lung injury I. The effects of X-irradiation on basal laminar proteoglycans. Rad. Res. 99: 410-419.

    Google Scholar 

  30. W. A. Rosenkrans, Jr. and D. P. Penney (1985). Cell-cell matrix interactions in induced lung injury II. x-irradiation mediated changes in specific basal laminar glycosaminoglycans. Int. J. Rad. Oncol. Biol. Phys. 11: 1629-1637.

    Google Scholar 

  31. T. Sakakura, A. Ishihara, and R. Yatani (1991). Tenascin in mammary gland development: from embryogenesis to carcinogenesis. Cancer Treat. Res. 53: 383-400.

    Google Scholar 

  32. E. J. Ehrhart, E. L. Gillette, and M. H. Barcellos-Hoff (1996). Immunohistochem ical evidence of rapid extracellular matrix remodeling after iron-particle irradiation of mouse mammary gland. Rad. Res. 145: 157-162.

    Google Scholar 

  33. R. Sawaya, P. J. Tofilon, S. Mohanam, F. Ali-Osman, L. A. Liotta, W. G. Stetler-Stevenson, and J. S. Rao (1994). Induction of tissue-type plasminogen activator and 72 kDa type IV collagenase by ionizing radiation in rat astrocytes. Int. J. Cancer 56: 214-218.

    Google Scholar 

  34. M. S. Stack, R. D. Gray, and S. V. Pizzo (1993). Modulation of murine B16F10 melanoma plasminogen activator production by a synthetic peptide derived from the laminin A chain. Cancer Res. 53(9): 1998-2004.

    Google Scholar 

  35. S. G. Shaughnessy, M. Whaley, R. M. Lafrenie, and F. W. Orr (1993). Walker 256 tumor cell degradation of extracellular matrices involves a latent gelatinase activated by reactive oxygen species. Arch. Biochem. Biophys. 304(2): 314-321.

    Google Scholar 

  36. G. P. Siegal, S. H. Barsky, V. P. Terranova, and L. A. Liotta (1981). Stages of neoplastic transformation of human breast tissue as monitored by dissolution of basement membrane components. An immunoperoxid ase study. Invasion Metastasis 1: 54-70.

    Google Scholar 

  37. W. Lewko, L. A. Liotta, M. S. Wicha, B. K. Vonderhaar, and W. R. Kidwell (1981). Sensitivity of N-nitrosomethylureainduced rat mammary tumors to cis-hydroxyproline, an inhibitor of collagen production. Cancer Res. 41: 2855-2862.

    Google Scholar 

  38. C. J. Sympson, M. J. Bissell, and Z. Werb (1995). Mammary gland tumor formation in transgenic mice overexpressing stromelysin-1. Sem. Cancer Biol. 6: 159-163.

    Google Scholar 

  39. E. L. Alpen, P. Powers-Risius, S. B. Curtis, and R. DeGuzman (1993). Tumorigenic potential of high-Z, high LET charged-particle radiations. Rad. Res. 136: 382-391.

    Google Scholar 

  40. K. Miyazono and C.-H. Heldin (1991). Latent forms of TGF-β: Molecular structure and mechanisms of activation. In G. R. Bock and J. Marsh (eds.), Clinical Applications of TGF-β. John Wiley, Chichester, pp. 81-92.

    Google Scholar 

  41. M. H. Barcellos-Hoff (1996). Latency and activation in the regulation of TGF-β. J. Mam. Gland Biol. Neoplasia 3(1): 353-363.

    Google Scholar 

  42. G. H. Smith, (1996). TGF-β and functional differentiation. J. Mam. Gland Biol. Neoplasia 1: 343-352.

    Google Scholar 

  43. M. H. Barcellos-Hoff, R. Derynck, M. L.-S. Tsang, and J. A. Weatherbee (1994). Transforming growth factor-β activation in irradiated murine mammary gland. J. Clin. Invest. 93: 892-899.

    Google Scholar 

  44. E. J. Ehrhart, A. Carroll, P. Segarini, M. L.-S. Tsang, and M. H. Barcellos-Hoff (1997). Latent transforming growth factor-β activation in situ: Quantitative and functional evidence following low dose irradiation. FASEB J. 11: 991-1002.

    Google Scholar 

  45. A. B. Roberts, M. B. Sporn, R. K. Assoian, J. M. Smithe, N. S. Roche, L.M. Wakefield, U. I. Heine, L. A. Liotta, V. Falanga, J. H. Kehrl, and A. S. Fauci (1986). Transforming growth factor type β: Rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc. Natl. Acad. Sci. U.S.A. 83: 4167-4171.

    Google Scholar 

  46. M. Reiss and M. H. Barcellos-Hoff (1997). Transforming growth factor-β in breast cancer: A working hypothesis. Br. Cancer Res. Treat. 45: 81-95.

    Google Scholar 

  47. T. M. Fynan and M. Reiss (1993). Resistance to inhibition of cell growth by transforming growth factor-β and its role in oncogenesis. Critical Rev. Oncogen. 4: 493-540.

    Google Scholar 

  48. P. Barrett-Lee, M. Travers, Y. Luqmani, and R. C. Coombes (1990). Transcripts for transforming growth factors in human breast cancer: clinical correlates. Brit. J. Cancer 61: (4)612-617.

    Google Scholar 

  49. A. Butta, K. MacLennan, K. C. Flanders, N. P. M. Sacks, I. Smith, A. McKinna, M. Dowsett, L. M. Wakefield, M. B. Sporn, M. Baum, and A. A. Colletta (1992). Induction of transforming growth factor β1 in human breast cancer in vivo following tamoxifen treatment. Cancer Res. 52: 4261-4264.

    Google Scholar 

  50. J. Godden, C. Porteous, W. D. George, and D. J. Kerr (1993). Bioassay of transforming gorwht factor-β activity in acidic protein extracts from primary breast cancer specimens. Anti-cancer Res. 13: 427-431.

    Google Scholar 

  51. C. Knabbe, M. E. Lippman, L. M. Wakefield, K. C. Flanders, A. Dasid, R. Derynck, and R. B. Dickson (1987). Evidence that transforming growth factor-β is a hormonally regulated negative growth factor in human breast cancer cells.Cell 48: 417-428.

    Google Scholar 

  52. A. A. Colletta, L. M. Wakefield, F. V. Howell, D. Danielpour, M. Baum, and M. B. Sporn (1991). The growth inhibition of human breast cancer cells by a novel synthetic progestin involoves the induction of transforming growth factor beta. J. Clin. Invest. 87: 277-283.

    Google Scholar 

  53. M. Guerrin, H. Prats, P. Mazars, and A. Valette (1992). Antiproliferative effect of phorbol esters on MCF-7 human breast adenocarcinoma cells: relationship with enhanced expression of transforming growth-factor β1. Biochimica et Biophysica Acta 1137: 116-120.

    Google Scholar 

  54. C. L. Arteaga, R. J. Coffey, T. C. Dugger, C. M. McCutchen, H. L. Moses, and R. M. Lyons (1990). Growth stimulation of human breast cancer cells with anti-transforming growth factor βantibodies: Evidence for negative autocrine regulation by transforming growth factor β. Cell Growth Differ. 1: 367-374.

    Google Scholar 

  55. R. L. Jirtle, J. D. Haag, E. A. Ariazi, and M. N. Gould (1993). Increased mannose 6-phosphate/insul in-like growth fator II receptor and transforming growth factor β1 levels during monoterpene-ind uced regresssion of mammary tumors. Cancer Res. 53: 3849-3852.

    Google Scholar 

  56. D. R. Welch, A. Fabra, and M. Nakajima (1990). Transforming growth factor β stimulates mammary adenocarcinoma cell invasion and metastatic potential. PNAS 87: 7678-7682.

    Google Scholar 

  57. J. D. Croxtall, A. Jamil, M. Ayub, A. A. Colletta, and J. O. White (1992). TGFβ stimulation of endometrial and breastcancer cell growth. Int. J. Cancer 50: 822-827.

    Google Scholar 

  58. S. M. Gorsch, V. A. Memoli, T. A. Stukel, L. I. Gold, and B. A. Arrick (1992). Immunohistochemical staining for transforming growth factor β1 associates with disease progression in human breast cancer. Cancer Res. 52: 6949-6952.

    Google Scholar 

  59. B. K. McCune, B. R. Mullin, K. C. Flanders, W. J. Jaffurs, L. T. Mullen, and M. B. Sporn (1992). Localization of transforming growth factor-β isotypes in lesions of the human breast. Human Pathol. 23(1): 13-20.

    Google Scholar 

  60. B. I. Dalal, P. A. Keown, and A. H. Greenberg (1993). Immunocytochemical localization of secreted transforming growth factor-β1 to the advancing edges of primary tumors and to lymph node metastases of human mammary carcinoma. Am. J. Pathol. 143: 381-389.

    Google Scholar 

  61. I. Wakefield, A. A. Colletta, B. K. McCune, and M. B. Sporn, Roles for transforming growth factors-β in the genesis, prevention and treatment of breast cancer. In R. B. Dickson and M. E. Lippman, (eds.), Genes, Oncogens, and Hormones: Advances in Cellular and Molecular Biology of Breast Cancer Kluwer Academic Publishers, Boston, pp. 97-136.

  62. D. F. Pierce, A. E. Gorska, A. Chythil, K. S. Meise, D. L. Page, R. J. Coffey, Jr., and H. L. Moses (1995). Mammary tumor suppression by transforming growth factor β1 transgene expression. Proc. Natl. Acad. Sci. U.S.A. 92: 4254-4258.

    Google Scholar 

  63. E. P. Bottinger, J. L. Jakubczak, D. C. Haines, K. Bagnall, and L. M. Wakefield (1997). Transgenic mice overexpressing a dominant-negati ve mutant type II transforming growth factor βreceptor show enhanced tumorigenesis in the mammary gland and lung in response to the carcinogen 7,12-dimthylb enz[a]-anthracene. Cancer Res. 57: 5564-5570.

    Google Scholar 

  64. W. Cui, D. J. Fowlis, S. Bryson, E. Duffie, H. Ireland, A. Balmain, and R. J. Akhurst (1996). TGF-β inhibits the formation of benign skin tumors, but enhances progression to invasive spindle carcinomas in transgenic mice. Cell 86(4): 531-542.

    Google Scholar 

  65. R. A. Ignotz and J. Massague (1987). Cell adhesion protein receptors as targets for transforming growth factor-β action. Cell 51: 189-197.

    Google Scholar 

  66. Y. Sato, F. Okada, M. Abe, T. Seguchi, M. Kuwano, S. Sato, A. Furuya, N. Hanai, and T. Tamaoki (1993). The mechanism for the activation of latent TGF-β during co-culture of endothelial cells and smooth muscle cells: cell-type specific targeting of latent TGF-β to smooth muscle cells. J. Cell Biol. 123(5): 1249-1254.

    Google Scholar 

  67. M. Terzaghi and P. Nettesheim (1979). Dynamics of neoplastic development in carcinogen-exposed tracheal mucosa. Cancer Res. 39: 3004-3010.

    Google Scholar 

  68. R. J. M. Fry, R. D. Ley, D. Grube, and E. Staffeldt (1982). Studies on the multistage nature of radiation carcinogenesis. Carcinogen 7: 155-165.

    Google Scholar 

  69. R. L. Ullrich and J. B. Storer (1979). Influence of gammairradiation on the development of neoplastic disease in mice. Rad. Res. 80: 325-342.

    Google Scholar 

  70. R. L. Ullrich (1986). The rate of progression of radiation-transformed mammary epithelial cells is enhanced after lowdose-rate neutron irradiation. Rad. Res. 105: 68-75.

    Google Scholar 

  71. R. Parsons, G.-M. Li, M. J. Longley, W. Fanc, N. Papadopoulos, J. Jen, A. de la Chapelle, K. W. Kinzler, B. Vogelstein, and P. Modrich (1993). Hypermutability and mismatch repair deficiency in RER+ tumor cells. Cell 75: 1227-1236.

    Google Scholar 

  72. R. Parsons, G. M. Li, M. Longley, P. Modrich, L. B., T. Berk, S. R. Hamilton, K. W. Kinzler, and B. Vogelstein (1995). Mismatch repair deficiency in phenotypically normal human cells. Science 268: 738-740.

    Google Scholar 

  73. S. Markowitz, J. Wang, L. Myeroff, R. Parsons, L. Sun, R. S. Fan, E. Zborowska, K. W. Kinzler, B. Vogelstein, M. Brattain, and J. K. Willson (1995). Inactivation of the type II TGF-β receptor in colon cancer cells with microsatellite instability. Science 268: 1336-1338.

    Google Scholar 

  74. E. J. Bernhard, S. B. Gruber, and R. J. Muschel (1994). Direct evidence linking expression of matrix metalloproteinase 9(92kDa gelatinase/collage nase) to the metastatic phenotype in transformed rat embryo cells. Proc. Natl. Acad. Sci. U.S.A. 91: 4293-4297.

    Google Scholar 

  75. G. B. Silberstein and C.W. Daniel (1982). Elvax 40P implants, sustained local release of bioactive molecules influencing the mammary ductal development. Devel. Biol. 93: 272-278.

    Google Scholar 

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Barcellos-Hoff, M.H. The Potential Influence of Radiation-Induced Microenvironments in Neoplastic Progression. J Mammary Gland Biol Neoplasia 3, 165–175 (1998). https://doi.org/10.1023/A:1018794806635

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