Animal Models of Bone Metastasis

  • Thomas J. Rosol
  • Sarah H. Tannehill-Gregg
  • Stephanie Corn
  • Abraham Schneider
  • Laurie K. McCauley
Part of the Cancer Treatment and Research book series (CTAR, volume 118)


Animal models are important tools to investigate the pathogenesis and develop treatment strategies for bone metastases as they occur in humans. However, there are few spontaneous models of bone metastasis despite the fact that rodents (rats and mice) and other animals, such as dogs and cats, often spontaneously develop cancer. Therefore, most experimental models of bone metastasis in rodents require injection or implantation of neoplastic cells into orthotopic locations, bones, or the left ventricle of the heart.


Prostate Cancer Multiple Myeloma Bone Metastasis Prostate Gland Mouse Mammary Tumor Virus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alsina, M., Boyce, B., Devlin, R. D., Anderson, J. L., Craig, F., Mundy, G.R. and Roodman, G. D. (1996). Development of an in vivo model of human multiple myeloma bone disease. American Cancer Society. American Cancer Society Cancer Facts and Figures 2002. worldwide web. 2003. Ref Type: Electronic CitationGoogle Scholar
  2. Anidjar, M., Villette, J. M., Devauchelle, P., Delisle, F., Cotard, J. P., Billotey, C., CochandPriollet, B., Copin, H., Barnoux, M., Triballeau, S., Rain, J. D., Fiet, J., Teillac, P., Berthon, P. and Cussenot, O. (2001) In vivo model mimicking natural history of dog prostate cancer using DPC-1, a new canine prostate carcinoma cell line. The Prostate 46: 2–10.PubMedGoogle Scholar
  3. Aquilina, J. W., McKinney, L., Pacelli, A., Richman, L. K., Waters, D. J., Thompson, I., Burghardt, W. F., Jr. and Bostwick, D.G. (1998) High grade prostatic intraepithelial neoplasia in military working dogs with and without prostate cancer. The Prostate 36: 189–193.PubMedGoogle Scholar
  4. Arai, C., Ono, M., Une, Y., Shirota, K., Watanabe, T. and Nomura, Y. (1991) Canine renal carcinoma with extensive bone metastasis. Journal of Veterinary Medical Science 53: 495–497.PubMedGoogle Scholar
  5. Arguello, F., Baggs, R. B. and Frantz, C. N. (1988) A murine model of experimental metastasis to bone and bone marrow. Cancer Research 48: 6876–6881.PubMedGoogle Scholar
  6. Arnold, J. and Eustis, S. L. 1991. “Tumor incidences in Fischer 344 rats: NTP historical data.” In: Haseman, J. K. (ed.), Pathology of the Fischer Rat. Academic Press, pp. 555–564.Google Scholar
  7. Bataille, R. 1996. “Human myeloma-induced bone changes” In: Gahrton, G. and Durie, B. G. M. (eds.), Multiple Myeloma. Arnold, pp. 51–54.Google Scholar
  8. Blomme, E. A., Dougherty, K. M., Pienta, K. J., Capen, C. C., Rosol, T. J. and McCauley, L. K. (1999) Skeletal metastasis of prostate adenocarcinoma in rats: morphometric analysis and role of parathyroid hormone-related protein. Prostate 39: 187–197.PubMedGoogle Scholar
  9. Cardiff, R. D., Anver, M. R., Gusterson, B. A., Hennighausen, L., Jensen, R. A., Merino, M. J., Rehm, S., Russo, J., Tavassoli, F. A., Wakefield, L. M., Ward, J. M. and Green, J. E. (2000) The mammary pathology of genetically engineered mice: the consensus report and recommendations from the Annapolis meeting. Oncogene 19: 968–988.PubMedGoogle Scholar
  10. Centers for Disease Control (1995) Deaths from melanoma-United States, 1973-1992. MMWR Morbidity and Mortality Weekly Report 44: 337, 343-347.Google Scholar
  11. Chandra, M., Riley, M.G. and Johnson, D. E. (1993) Spontaneous renal neoplasms in rats. Journal of Applied Toxicology 13: 109–116.PubMedGoogle Scholar
  12. Cher, M. L. (2001) Mechanisms governing bone metastasis in prostate cancer. Current Opinions of Urology 11: 483–488.Google Scholar
  13. Clements, J. A. (1989) The glandular kallikrein family of enzymes: tissue-specific expression and hormonal regulation. Endocrine Reviews 10: 393–419.PubMedGoogle Scholar
  14. Cohen, P. R. (2001) Metastatic tumors to the nail unit: subungual metastases. Dermatology Surgery 27: 280–293.Google Scholar
  15. Cohn-Cedermark, G., Mansson-Brahme, E., Rutqvist, L. E., Larsson, O., Singnomklao, T. and Ringborg, U. (1999) Metastatic patterns, clinical outcome, and malignant phenotype in malignant cutaneous melanoma. Acta Oncology 38: 549–557.Google Scholar
  16. Coleman, R. E. (1997) Skeletal complications of malignancy. Cancer 80: 1588–1594.PubMedGoogle Scholar
  17. Corey, E., Quinn, J. E., Bladou, F., Brown, L. G., Roudier, M. P., Brown, J. M., Buhler, K.R. and Vessella, R. L. (2002) Establishment and characterization of osseous prostate cancer models: intra-tibial injection of human prostate cancer cells. Prostate 52: 20–33.PubMedGoogle Scholar
  18. Cornell, K. K., Bostwick, D. G., Cooley, D. M., Hall, G., Harvey, H. J., Hendrick, M. J., Pauli, B. U., Render, J. A., Stoica, G., Sweet, D.C. and Waters, D. J. (2000) Clinical and pathologic aspects of spontaneous canine prostate carcinoma: a retrospective analysis of 76 cases. Prostate 45: 173–183.PubMedGoogle Scholar
  19. Costa, G. L., Sandora, M. R., Nakajima, A., Nguyen, E. V., Taylor-Edwards, C., Slavin, A. J., Contag, C. H., Fathman, C.G. and Benson, J. M. (2001) Adoptive immunotherapy of experimental autoimmune encephalomyelitis via T cell delivery of the IL-12 p40 subunit. Journal of Immunology 167: 2379–2387.Google Scholar
  20. Croese, J. W., Vas Nunes, C. M., Radl, J., Enden-Vieveen, M. H., Brondijk, R. J. and Boersma, W. J. (1987) The 5T2 mouse multiple myeloma model: characterization of 5T2 cells within the bone marrow. British Journal of Cancer 56: 555–560.PubMedGoogle Scholar
  21. Cunha, G. R., Donjacour, A. A., Cooke, P. S., Mee, S., Bigsby, R. M., Higgins, S.J. and Sugimura, Y. (1987) The endocrinology and developmental biology of the prostate. Endocrine Reviews 8: 338–362.PubMedGoogle Scholar
  22. Edinger, M., Sweeney, T. J., Tucker, A. A., Olomu, A. B., Negrin, R. S. and Contag, C. H. (1999) Noninvasive assessment of tumor cell proliferation in animal models. Neoplasia 1: 303–310.PubMedGoogle Scholar
  23. Ellis, W. J., Vessella, R. L., Buhler, K. R., Bladou, F., True, L. D., Bigler, S. A., Curtis, D. and Lange, P. H. (1996) Characterization of a novel androgen-sensitive, prostate-specific antigen-producing prostatic carcinoma xenograft: LuCaP 23. Clinical Cancer Research 2: 1039–1048.PubMedGoogle Scholar
  24. Everitt, J. I., Goldsworthy, T. L., Wolf, D.C. and Walker, C. L. (1992) Hereditary renal cell carcinoma in the Eker rat: a rodent familial cancer syndrome. Journal of Urology 148: 1932–1936.PubMedGoogle Scholar
  25. Evison, G., Pizey, N. and Roylance, J. (1981) Bone formation associated with osseous metastases from bladder carcinoma. Clinical Radiology 32: 303–309.PubMedGoogle Scholar
  26. Foster, B. A. and Greenberg, N. M. (2001) New model of bone metastasis for prostate cancer: Cell lines derived from a bone metastasis in TRAMP. Proceedings of the American Association for Cancer Research 42: 140 (abstract).Google Scholar
  27. Gado, K., Silva, S., Paloczi, K., Domjan, G. and Falus, A. (2001) Mouse plasmacytoma: an experimental model of human multiple myeloma. Haematologica 86: 227–236.PubMedGoogle Scholar
  28. Galasko, C. S. (1981a) Monitoring of bone metastases. Schweiz. Med. Wochenschr. 111: 1873–1875.PubMedGoogle Scholar
  29. Galasko, C. S. (1982) Mechanisms of lytic and blastic metastatic disease of bone. Clin Orthop 169: 20–27.PubMedGoogle Scholar
  30. Galasko, C. S. B. (1981b). “The anatomy and pathways of skeletal metastases” In: Weiss, L. and Gilbert, A. H. (eds.), Bone Metastases. GK Hall, pp. 49–63.Google Scholar
  31. Galmarini, C. M., Kertesz, A., Oliva, R., Porta, J. and Galmarini, F. C. (1998) Metastasis of bronchogenic carcinoma to the thumb. Medical Oncology 15: 282–285.PubMedGoogle Scholar
  32. Goldschmidt, M. H. and Hendrick, M. J. 2002. “Tumors of the Skin and Soft Tissues” In: Meuten, D.J. (ed.), Tumors in Domestic Animals Iowa State Press, pp. 45–117.Google Scholar
  33. Gottfried, S. D., Popovitch, C. A., Goldschmidt, M.H. and Schelling, C. (2000) Metastatic digital carcinoma in the cat: a retrospective study of 36 cats (1992-1998). Journal of American Animal Hospital Association 36: 501–509.Google Scholar
  34. Guise, T. A. (2000) Molecular mechanisms of osteolytic bone metastases. Cancer 88: 2892–2898.PubMedGoogle Scholar
  35. Guise, T. A., Yin, J. J., Thomas, R. J., Dallas, M., Cui, Y. and Gillespie, M. T. (2002) Parathyroid hormone-related protein (PTHrP)-(l-139) isoform is efficiently secreted in vitro and enhances breast cancer metastasis to bone in vivo. Bone 30: 670–676.PubMedGoogle Scholar
  36. Hahn, K.A. and McEntee, M. F. (1997) Primary lung tumors in cats: 86 cases (1979-1994). Journal of American Veterinary Medical Association 211: 1257–1260.Google Scholar
  37. Haseman, J. K., Elwell, M. R. and Hailey, J. R. (1999). “Neoplasm Incidences in B6C3F1 Mice: NTP Historical Data” In: Maronpot, R. R., Boorman, G. A. and Gaul, B.W. (eds.), Pathology of the Mouse. Cache River Press, pp. 679–689.Google Scholar
  38. Hastings, R. H., Burton, D. W., Summers-Torres, D., Quintana, R., Biederman, E. and Deftos, L. J. (2000) Splenic, thymic, bony and lymph node metastases from orthotopic human lung carcinomas in immunocompromised mice. Anticancer Research 20: 3625–3629.PubMedGoogle Scholar
  39. Hawrysz, D. J. and Sevick-Muraca, E. M. (2000) Developments toward diagnostic breast cancer imaging using near-infrared optical measurements and fluorescent contrast agents. Neoplasia. 2:388–417.PubMedGoogle Scholar
  40. Hiraga, T., Nakajima, T. and Ozawa, H. (1995) Bone resorption induced by a metastatic human melanoma cell line. Bone 16: 349–356.PubMedGoogle Scholar
  41. Hoffman, R. M. (1998) Orthotopic transplant mouse models with green fluorescent proteinexpressing cancer cells to visualize metastasis and angiogenesis. Cancer Metastasis Review. 17: 271–277.Google Scholar
  42. Hoffman, R. M. (1999) Orthotopic metastatic mouse models for anticancer drug discovery and evaluation: a bridge to the clinic. Investigating New Drugs 17: 343–359.Google Scholar
  43. Hoffman, R. M. (2001) Visualization of GFP-expressing tumors and metastasis in vivo. Biotechniques 30: 1016.PubMedGoogle Scholar
  44. Howard, R. B., Mullen, J. B., Pagura, M. E. and Johnston, M. R. (1999) Characterization of a highly metastatic, orthotopic lung cance model in the nude rat. Clinical Experimental Metastasis 17: 157–162.PubMedGoogle Scholar
  45. Huss, W. J., Maddison, L. A. and Greenberg, N. M. (2001) Autochthonous mouse models for prostate cancer: past, present and future. Semin. Cancer Biology 11: 245–260.Google Scholar
  46. Iguchi, H., Tanaka, S., Ozawa, Y., Kashiwakuma, T., Kimura, T., Hiraga, T., Ozawa, H. and Kono, A. (1996) An experimental model of bone metastasis by human lung cancer cells: the role of parathyroid hormone-related protein in bone metastasis. Cancer Research 56: 4040–4043.PubMedGoogle Scholar
  47. Ip, C. (1996) Mammary tumorigenesis and chemoprevention studies in carcinogen-treated rats. Journal of Mammary Gland Biology Neoplasia 1: 37–47.Google Scholar
  48. Isaacs, J. T. (1984) The aging ACI/Seg versus Copenhagen male rat as a model system for the study of prostatic carcinogenesis. Cancer Research 44: 5785–5796.PubMedGoogle Scholar
  49. Iwasaki, T., Yamashita, K., Tsujimura, T., Kashiwamura, S., Tsutsui, H., Kaisho, T., Sugihara, A., Yamada, N., Mukai, M., Yoneda, T., Okamura, H., Akedo, H. and Terada, N. (2002) Interleukin-18 inhibits osteolytic bone metastasis by human lung cancer cells possibly through suppression of osteoclastic bone-resorption in nude mice. Journal of Immunotherapy 25 Suppl 1: S52–S60.PubMedGoogle Scholar
  50. Izumi, K., Kitaura, K., Chone, Y., Tate, H., Nakagawa, T., Suzuki, Y. and Matsumoto, K. (1994) Spontaneous renal cell tumors in Long-Evans Cinnamon rats. Japananese Journal of Cancer Research 85: 563–566.Google Scholar
  51. Jackson, E. L. and Jacks, T. MMHC The mouse models of human cancers consortium. worldwide web. 2003. Ref Type: Electronic CitationGoogle Scholar
  52. Jacobs, R. M., Messick, J.B. and Valli, V. E. (2002). “Tumors of the Hemolymphatic System” In: Meuten, D. J. (ed.), Tumors in Domestic Animals Iowa State Press, pp. 119–198.Google Scholar
  53. Johnston, M. R., Mullen, J. B., Pagura, M.E. and Howard, R. B. (2001) Validation of an orthotopic model of human lung cancer with regional and systemic metastases. Annals of Thoracic Surgery 71: 1120–1125.PubMedGoogle Scholar
  54. Kaighn, M. E., Narayan, K. S., Ohnuki, Y., Lechner, J. F. and Jones, L. W. (1979) Establishment and characterization of a human prostatic carcinoma cell line (PC-3). Invest Urology 17: 16–23.Google Scholar
  55. Kanno, J. 1989. “Melanocytic tumors, skin, mouse” In: Jones, T. C. (ed.), Integument and Mammary Glands Springer-Verlag, pp. 63–69.Google Scholar
  56. Kjonniksen, I., Nesland, J. M., Pihl, A. and Fodstad, O. (1990) Nude rat model for studying metastasis of human tumor cells to bone and bone marrow. Journal of National Cancer Institute 82: 408–412.Google Scholar
  57. Klein-Szanto, A. J., Silvers, W. K. and Mintz, B. (1994) Ultraviolet radiation-induced malignant skin melanoma in melanoma-susceptible transgenic mice. Cancer Research 54: 4569–4572.PubMedGoogle Scholar
  58. Kligman, L. H. and Elenitsas, R. (2001) Melanoma induction in a hairless mouse with shortterm application of dimethylbenz[a]anthracene. Melanoma Research 11: 319–324.PubMedGoogle Scholar
  59. Koutsilieris, M. (1992) PA-III rat prostate adenocarcinoma cells (review). In Vivo 6: 199–203.PubMedGoogle Scholar
  60. Kuo, T. H., Kubota, T., Watanabe, M., Furukawa, T., Teramoto, T., Ishibiki, K., Kitajima, M. and Hoffman, R. M. (1993) Early resection of primary orthotopically-growing human colon tumor in nude mouse prevents liver metastasis: further evidence for patient-like hematogenous metastatic route. Anticancer Research 13: 293–297.PubMedGoogle Scholar
  61. Landis, S. H., Murray, T., Bolden, S. and Wingo, P. A. (1998) Cancer statistics, 1998. CA Cancer J. Clin. 48: 6–29.PubMedGoogle Scholar
  62. Leav, I., Schelling, K. H., Adams, J. Y., Merk, F. B. and Alroy, J. (2001a) Role of canine basal cells in postnatal prostatic development, induction of hyperplasia, and sex hormonestimulated growth; and the ductal origin of carcinoma. The Prostate 48: 210–224.PubMedGoogle Scholar
  63. Leav, I., Schelling, S. H. and Merk, F. B. (2001b). “Age-related and sex hormone-induced changes in the canine prostate” In: Mohr, U., Carlton, W. W., Dungworth, D. L., Benjamin, SA., Capen, C. C. and Hahn, F.A. (eds.), Pathobiology of the Aging Dog. Iowa State Press, pp. 310–329.Google Scholar
  64. Lelekakis, M., Moseley, J. M., Martin, T. J., Hards, D., Williams, E., Ho, P., Lowen, D., Javni, J., Miller, F. R., Slavin, J. and Anderson, R. L. (1999) A novel orthotopic model of breast cancer metastasis to bone. Clinical Exp Metastasis 17: 163–170.Google Scholar
  65. LeRoy, B. E., Bahnson, R. R. and Rosol, T. J. (2002) Canine prostate induces new bone formation in mouse calvaría: A model of osteoinduction by prostate tissue. The Prostate 50: 104–111.PubMedGoogle Scholar
  66. Linde-Sipman, J. S. and van den Ingh, T. S. (2000) Primary and metastatic carcinomas in the digits of cats. Vet Q. 22: 141–145.PubMedGoogle Scholar
  67. Liu, B., Wang, Y., Melana, S. M., Pelisson, I., Najfeld, V., Holland, J. F. and Pogo, B. G. (2001) Identification of a proviral structure in human breast cancer. Cancer Research 61: 1754–1759.PubMedGoogle Scholar
  68. Lucia, M. S., Bostwick, D. G., Bosland, M., Cockett, A. T., Knapp, D. W., Leav, I., Pollard, M., Rinker-Schaeffer, C., Shirai, T. and Watkins, B. A. (1998) Workgroup I: rodent models of prostate cancer. Prostate 36: 49–55.PubMedGoogle Scholar
  69. Lucke, V. M. and Kelly, D. F. (1976) Renal carcinoma in the dog. Veterinary Pathology 13: 264–276.PubMedGoogle Scholar
  70. Mai, K. T., Landry, D. C, Robertson, S. J., Commons, A. S., Burns, B. F., Thijssen, A. and Collins, J. (2001) A comparative study of metastatic renal cell carcinoma with correlation to subtype and primary tumor. Pathology Research Pract. 197: 671–675.Google Scholar
  71. Malkinson, A. M. (2001) Primary lung tumors in mice as an aid for understanding, preventing, and treating human adenocarcinoma of the lung. Lung Cancer 32: 265–279.PubMedGoogle Scholar
  72. Maurer-Gebhard, M., Schmidt, M., Azemar, M., Stocklin, E., Wels, W. and Groner, B. (1999) A novel animal model for the evaluation of the efficacy of drugs directed against the ErbB2 receptor on metastasis formation. Hybridoma 18: 69–75.PubMedGoogle Scholar
  73. Meuten, D. J. 2002. “Tumors of the Urinary System” In: Meuten, D. J. (ed.), Tumors of Domestic Animals. Iowa State Press, pp. 509–546.Google Scholar
  74. Meyers, M. L. and Balch, C. M. 1998. “Diagnosis and treatment of metastatic melanoma.” In: Balch, C. M., Houghton, A. N., Sober, A. J. and Soong, S. J. (eds.), Cutaneous Melanoma. Quality Medical Publishing, Inc., pp. 325–372.Google Scholar
  75. Miki, T., Yano, S., Hanibuchi, M. and Sone, S. (2000) Bone metastasis model with multiorgan dissemination of human small-cell lung cancer (SBC-5) cells in natural killer cell-depleted SCID mice. Oncology Research 12: 209–217.PubMedGoogle Scholar
  76. Misdorp, W. 2002. “Tumors of the Mammary Gland” In: Meuten, D. J. (ed.), Tumors in Domestic Animals. Iowa State Press, pp. 575–606.Google Scholar
  77. Mohammad, K. S., Yin, J. J., Grubbs, B. G., Cui, Y., Padley, R. and Guise, T. A. (2001) Endothelin-1 (ET-1) mediates pathological but not normal bone remodeling [Abstract]. Journal of Bone and Mineral Research 16 (Suppl. 1): S453.Google Scholar
  78. Namikawa, R. and Shtivelman, E. (1999) SCID-hu mice for the study of human cancer metastasis. Cancer Chemotherapy. Pharmacology 43 Suppl: S37–S41.Google Scholar
  79. Nemeth, J. A., Harb, J. F., Barroso, U., Jr., He, Z., Grignon, D. J. and Cher, M. L. (1999) Severe combined immunodeficient-hu model of human prostate cancer metastasis to human bone. Cancer Research 59: 1987–1993.PubMedGoogle Scholar
  80. Nemoto, H., Rittling, S. R., Yoshitake, H., Furuya, K., Amagasa, T., Tsuji, K., Nifuji, A., Denhardt, D. T. and Noda, M. (2001) Osteopontin deficiency reduces experimental tumor cell metastasis to bone and soft tissues. Journal of Bone and Mineral Research 16: 652–659.PubMedGoogle Scholar
  81. Osterborg, A. and Mellstedt, H. (1996). “Clinical features and staging” In: Gahrton, G. and Durie, B. G. M. (eds.), Multiple Myeloma. Arnold, pp. 98–107.Google Scholar
  82. Paget, S. (1889) The distribution of secondary growths in cancer of the breast. Lancet 1: 571–573.Google Scholar
  83. Pollard, M. (1998 a) Dihydrotestosterone prevents spontaneous adenocarcinomas in the prostate-seminal vesicle in aging L-W rats. The Prostate 36: 168–171.PubMedGoogle Scholar
  84. Pollard, M. (1998b) Lobund-Wistar rat model of prostate cancer in man. The Prostate 37: 1–4.PubMedGoogle Scholar
  85. Pollard, M. (1999) Prevention of prostate-related cancers in Lobund-Wistar rats. The Prostate 39: 305–309.PubMedGoogle Scholar
  86. Pollard, M., Luckert, P. H. and Snyder, D. L. (1989) The promotional effect of testosterone on induction of prostate-cancer in MNU-sensitized L-W rats. Cancer Letters 45: 209–212.PubMedGoogle Scholar
  87. Pollard, M., Wolter, W. R. and Sun, L. (2000) Prostate-seminal vesicle cancers induced in noble rats. The Prostate 43: 71–74.PubMedGoogle Scholar
  88. Radl, L, Punt, Y. A., Enden-Vieveen, M. H., Bentvelzen, P. A., Bakkus, M. H., van den Akker, T. W. and Benner, R. (1990) The 5T mouse multiple myeloma model: absence of c-myc oncogene rearrangement in early transplant generations. British Journal of Cancer 61: 276–278.PubMedGoogle Scholar
  89. Rice, B. W., Cable, M. D. and Nelson, M. B. (2001) In vivo imaging of light-emitting probes. Journal of Biomedical Opthamology 6: 432–440.Google Scholar
  90. Rosol, T. J. (2000) Pathogenesis of bone metastases: Role of tumor-related proteins. Journal of Bone and Mineral Research 15: 844–850.PubMedGoogle Scholar
  91. Rubens, R. D. and Coleman, R. E. (1995). “Bone Metastases” In: Abeloff, M. D., Armitage, J. O., Lichter, A. S. and Niederhuber, J. E. (eds.), Clinical Oncology. Churchill Livingstone, pp. 643–665.Google Scholar
  92. Schneider, A., Taboas, J. M., Krebsbach, P. H. and McCauley, L. K. (2002) An ectopic tissue engineered bone model to study hormonal responses in vivo [abstract]. Presented at the Third North American Symposium on Skeletal Complications of Malignancy, Bethesda, MD, April 25-27, 2002.Google Scholar
  93. Seely, J. C. and Boorman, G. A. (1999). “Mammary Gland and Specialized Sebaceous Glands” In: Maronpot, R. R., Boorman, G. A. and Gaul, B. W. (eds.), Pathology of the Mouse. Cache River Press, pp. 613–636.Google Scholar
  94. Shevrin, D. H., Kukreja, S. C., Ghosh, L. and Lad, T. E. (1988) Development of skeletal metastasis by human prostate cancer in athymic nude mice. Clinical Exp. Metastasis 6: 401–409.Google Scholar
  95. Stearns, M. E., Ware, J. L., Agus, D. B., Chang, C. J., Fidler, I. J., Fife, R. S., Goode, R., Holmes, E., Kinch, M. S., Peehl, D. M., Pretlow, T. G. and Thalmann, G. N. (1998) Workgroup 2: human xenograft models of prostate cancer. The Prostate 36: 56–58.PubMedGoogle Scholar
  96. Stoica, G., Koestner, A. and Capen, C. C. (1983) Characterization of N-ethyl-N-nitrosoureainduced mammary tumors in the rat. American Journal of Pathology 110: 161–169.PubMedGoogle Scholar
  97. Stoica, G., Koestner, A. and Capen, C. C. (1984) Neoplasms induced with high single doses of N-ethyl-N-nitrosourea in 30-day-old Sprague-Dawley rats, with special emphasis on mammary neoplasia. Anticancer Research 4:5–12.PubMedGoogle Scholar
  98. Sung, V., Cattell, D. A., Bueno, J. M., Murray, A., Zwiebel, J. A., Aaron, A. D. and Thompson, E. W. (1997) Human breast cancer cell metastasis to long bone and soft organs of nude mice: a quantitative assay. Clinical Experimental Metastasis 15: 173–183.PubMedGoogle Scholar
  99. Suwa, T., Nyska, A., Haseman, J. K., Mahler, J. F. and Maronpot, R. R. (2002) Spontaneous lesions in control B6C3F1 mice and recommended sectioning of male accessory sex organs. Toxicologic Pathology 30: 228–234.PubMedGoogle Scholar
  100. Suwa, T., Nyska, A., Peckham, J. C, Hailey, J. R., Mahler, J. F., Haseman, J. K. and Maronpot, R. R. (2001) A retrospective analysis of background lesions and tissue accountability for male accessory sex organs in Fischer-344 rats. Toxicologic Pathology 29: 467–478.PubMedGoogle Scholar
  101. Sweeney, T. J., Mailander, V., Tucker, A. A., Olomu, A. B., Zhang, W., Cao, Y., Negrin, R. S. and Contag, C. H. (1999) Visualizing the kinetics of tumor-cell clearance in living animals. Proceedings of the National Academy of Science U S A 96: 12044–12049.Google Scholar
  102. Tennant, T. R., Kim, H., Sokoloff, M. and Rinker, S. (2000) The Dunning model. The Prostate 43: 295–302.PubMedGoogle Scholar
  103. Tester, A. M., Sharp, J. A., Dhanesuan, N., Waltham, M. and Thompson, E. W. (2002) Correlation between extent of osteolytic damage and metastatic burden of human breast cancer metastasis in nude mice: real-time PCR quantitation. Clinical Exp. Metastasis 19: 377–383.Google Scholar
  104. Thalmann, G. N., Sikes, R. A., Wu, T. T., Degeorges, A., Chang, S. M., Ozen, M., Pathak, S. and Chung, L. W. (2000) LNCaP progression model of human prostate cancer: androgenindependence and osseous metastasis. The Prostate 44: 91–103.PubMedGoogle Scholar
  105. Urashima, M., Chen, B. P., Chen, S., Pinkus, G. S., Bronson, R. T., Dedera, D. A., Hoshi, Y., Teoh, G., Ogata, A., Treon, S. P., Chauhan, D. and Anderson, K. C. (1997) The development of a model for the homing of multiple myeloma cells to human bone marrow. Blood 90: 754–765.PubMedGoogle Scholar
  106. Vaezy, A. and Budson, D. C. (1978) Phalangeal metastases from bronchogenic carcinoma. Journal of the American Medical Association 239: 226–227.PubMedGoogle Scholar
  107. van der Pluijm, G., Sijmons, B., Vloedgraven, H., Deckers, M., Papapoulos, S. and Lowik, C. (2001) Monitoring metastatic behavior of human tumor cells in mice with species-specific polymerase chain reaction: elevated expression of angiogenesis and bone resorption stimulators by breast cancer in bone metastases. Journal of Bone and Mineral Research 16: 1077–1091.PubMedGoogle Scholar
  108. Varma, V. A. and Austin, G. E. (1990) Morphologic characterization of early prostatic carcinomas in the ACI rat: a light and electron microscopic study. Experimental Molecular Pathology 52: 202–211.Google Scholar
  109. Wang, M. and Stearns, M. E. (1991) Isolation and characterization of PC-3 human prostatic tumor sublines which preferentially metastasize to select organs in S.C.I.D. mice. Differentiation 48: 115–125.PubMedGoogle Scholar
  110. Waters, D. J., Hayden, D. W., Bell, F. W., Klausner, J. S., Qian, J. and Bostwick, D. G. (1997) Prostatic intraepithelial neoplasia in dogs with spontaneous prostate cancer. The Prostate 30: 92–97.PubMedGoogle Scholar
  111. Weber, K. L., Pathak, S., Multani, A. S. and Price, J. E. (2002) Characterization of a renal cell carcinoma cell line derived from a human bone metastasis and establishment of an experimental nude mouse model. Journal of Urology 168: 774–779.PubMedGoogle Scholar
  112. Wetterwald, A., van der, P. G., Que, I., Sijmons, B., Buijs, J., Karperien, M., Lowik, C. W., Gautschi, E., Thalmann, G. N. and Cecchini, M. G. (2002) Optical imaging of cancer metastasis to bone marrow: a mouse model of minimal residual disease. American Journal of Pathology 160: 1143–1153.PubMedGoogle Scholar
  113. Wu, T. T., Sikes, R. A., Cui, Q., Thalmann, G. N., Kao, C, Murphy, C. F., Yang, H., Zhau, H. E., Balian, G. and Chung, L. W. (1998) Establishing human prostate cancer cell xenografts in bone: induction of osteoblastic reaction by prostate-specific antigenproducing tumors in athymic and SCID/bg mice using LNCaP and lineage-derived metastatic sublines. International Journal Cancer 77: 887–894.Google Scholar
  114. Yang, M., Baranov, E., Moossa, A. R., Penman, S. and Hoffman, R. M. (2000) Visualizing gene expression by whole-body fluorescence imaging. Proceedings of the National Academy of Science U. S. A 97: 12278–12282.Google Scholar
  115. Yang, M., Hasegawa, S., Jiang, P., Wang, X., Tan, Y., Chishima, T., Shimada, H., Moossa, A. R. and Hoffman, R. M. (1998) Widespread skeletal metastatic potential of human lung cancer revealed by green fluorescent protein expression. Cancer Research 58: 4217–4221.PubMedGoogle Scholar
  116. Yang, M., Jiang, P., An, Z., Baranov, E., Li, L., Hasegawa, S., Al Tuwaijri, M., Chishima, T., Shimada, H., Moossa, A. R. and Hoffman, R. M. (1999) Genetically fluorescent melanoma bone and organ metastasis models. Clinical Cancer Research 5: 3549–3559.PubMedGoogle Scholar
  117. Yi, B., Williams, P. J., Niewolna, M., Wang, Y. and Yoneda, T. (2002) Tumor-derived platelet-derived growth factor-BB plays a critical role in osteosclerotic bone metastasis in an animal model of human breast cancer. Cancer Research 62: 917–923.PubMedGoogle Scholar
  118. Yoneda, T. (1997) Arterial microvascularization and breast cancer colonization in bone. Histology and Histopathology 12: 1145–1149.PubMedGoogle Scholar
  119. Yoneda, T. (2000) Cellular and molecular basis of preferential metastasis of breast cancer to bone. Journal of Orthopaedic Science 5: 75–81.PubMedGoogle Scholar
  120. Yoneda, T., Michigami, T., Yi, B., Williams, P. J., Niewolna, M. and Hiraga, T. (1999a) Use of bisphosphonates for the treatment of bone metastasis in experimental animal models. Cancer Treatment Review 25: 293–299.Google Scholar
  121. Yoneda, T., Williams, P. J., Myoi, A., Michigami, T. and Mbalaviele, G. (1999b). “Cellular and molecular mechanisms of development of skeletal metastases” In: Body, J-J. (ed.), Tumor Bone Diseases and Osteoporosis in Cancer Patients, Marcel Dekker, Inc., pp. 41–69.Google Scholar
  122. Yonou, H., Yokose, T., Kamijo, T., Kanomata, N., Hasebe, T., Nagai, K., Hatano, T., Ogawa, Y. and Ochiai, A. (2001) Establishment of a novel species-and tissue-specific metastasis model of human prostate cancer in humanized non-obese diabetic/severe combined immunodeficient mice engrafted with human adult lung and bone. Cancer Research 61: 2177–2182.PubMedGoogle Scholar
  123. Young, D. M., Fioravanti, J. L., Prieur, D. J. and Ward, J. M. (1976) Hypercalcemic VX-2 carcinoma in rabbits: a clinicopathologic study. Laboratory Investigations 35: 30–46.Google Scholar
  124. Zhang, J., Dai, J., Qi, Y., Lin, D. L., Smith, P., Strayhorn, C., Mizokami, A., Fu, Z., Westman, J. and Keller, E. T. (2001) Osteoprotegerin inhibits prostate cancer-induced osteoclastogenesis and prevents prostate tumor growth in the bone. Journal of Clinical Investigations 107: 1235–1244.Google Scholar
  125. Zhau, H. E., Li, C. L. and Chung, L. W. (2000) Establishment of human prostate carcinoma skeletal metastasis models. Cancer 88: 2995–3001.PubMedGoogle Scholar
  126. Zurcher, C. and Roholl, P. J. M. 1989. “Melanocytic tumors, rat” In: Jones, T. C. (ed.), Integument and Mammary Glands, Springer-Verlag, pp. 76–86.Google Scholar

Copyright information

© Springer Science+Business Media New York 2004

Authors and Affiliations

  • Thomas J. Rosol
    • 1
  • Sarah H. Tannehill-Gregg
    • 1
  • Stephanie Corn
    • 1
  • Abraham Schneider
    • 2
  • Laurie K. McCauley
    • 2
  1. 1.Department of Veterinary BiosciencesThe Ohio State UniversityColumbusUSA
  2. 2.Department of Periodontics, Prevention, and GeriatricsUniversity of MichiganAnn ArborUSA

Personalised recommendations