Orthotopic Metastatic Mouse Models of Prostate Cancer

  • Robert M. Hoffman
Part of the Cancer Metastasis – Biology and Treatment book series (CMBT, volume 10)


Orthotopic metastatic models of prostate cancer are reviewed here. Emphasis is placed on surgical orthotopic implantation models in nude mice. The advantages of surgical orthotopic implantation of tissue fragments are discussed with regard to resulting metastasis which reflect the clinical pattern of prostate cancer. The use of green Cancer statistics, luorescent protein and red fluorescent protein to image primary tumor growth and metastasis, including whole-body imaging of prostate cancer, is discussed. The application of the models for gene expression studies, drug discovery, and gene therapy is also reviewed.

Key words

prostate cancer cell lines surgical orthotopic implantation green fluorescent protein red fluorescent protein whole-body imaging metastasis drug discovery 


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  1. 1.
    Jemal A, Thomas A, Murray T, Thun M. Cancer statistics, 2002. CA Cancer J Clin 2002, 52:23–47.PubMedGoogle Scholar
  2. 2.
    Huggins C, Hodges CV. Studies on prostatic cancer. I. The effcts of castration, of estrogen and of androgen injections on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res 1941, 1:293–7.Google Scholar
  3. 3.
    Fu X, Herrera H, Hoffman RM. Orthotopic growth and metastasis of human prostate carcinoma in nude mice after transplantation of histologically intact tissue. Int J Cancer 1992, 52:987–0.PubMedGoogle Scholar
  4. 4.
    Crawford ED, Eisenberger MA, McLeod DG, Spaulding JT, Benson R, Dorr FA. A controlled trial of leuprolide with and without flutamide in prostate carcinoma. N Engl J Med 1989, 321:419–24.PubMedGoogle Scholar
  5. 5.
    Stamey TA, McNeal JE. Adenocarcinoma of the prostate, In: Campbell’s Urology, 6th Ed. Walsh PC, Retik AB, Stamey TA, Vaughn ED Jr., eds, Philadelphia: W.B. Saunders, 1992.Google Scholar
  6. 6.
    An Z, Wang X, Geller J, Moossa AR, Hoffman RM. Surgical orthotopic implantation allows high lung and lymph node metastatic expression of human prostate carcinoma cell line PC-3 in nude mice. Prostate 1998, 34:169–74.PubMedGoogle Scholar
  7. 7.
    Nakamuto T, Chang C, Li A, Chokak G. Basic fibroblast growth factor in human prostate cancer cells. Cancer Res 1992, 52:571–7.Google Scholar
  8. 8.
    Ware JL. Prostate tumor progression and metastasis. Biochem Biophys Acta Rev Cancer 1987, 907:279–98.Google Scholar
  9. 9.
    Arnold W, Kopf-Maier P, Micheel B, eds, Immunodeficient Animals: Models for Cancer Research. Basel: Karger, 1996.Google Scholar
  10. 10.
    Rygaard J, Povlsen CO. Heterotransplantation of a human malignant tumour to “nude” mice. Acta Pathol Microbiol Scand 1969, 77:758–60.PubMedGoogle Scholar
  11. 11.
    Horoszewicz J, Leong S, Kawinski E, Karr J, Rosenthal H, Chu T et al. LNCap model of human prostatic carcinoma. Cancer Res 1983, 43:1809–11.PubMedGoogle Scholar
  12. 12.
    Stone KR, Mickey D, Wunderli H, Mickey G, Paulson D. Isolation of a human prostate carcinoma cell line (DU-145). Int J Cancer 1978, 21:274–81.PubMedGoogle Scholar
  13. 13.
    Kaighn M, Narayan K, Ohnuki Y, Lechner J, Jones LW. Establishment and characterization of a human prostatic carcinoma cell line (PC-3). Invest Urol 1979, 17:1623.Google Scholar
  14. 14.
    Kozlowski J, McEwan L, Keer H, Sensibar J, Sherwood ER, Lee C et al. Prostate cancer, the invasive phenotype: Application of new in vivo, in vitro approaches, pp. 189–231. In: Tumor Progression, Metastasis. Fidler IJ, Nicholson G, eds, New York: Alan R. Liss, 1988.Google Scholar
  15. 15.
    Dunning WF. Prostate cancer in the rat. Nat Cancer Inst Monogr 1963, 12:351–69.PubMedGoogle Scholar
  16. 16.
    Ware JJ, Paulson DF, Mickey GH, Webb KS. Spontaneous metastasis of cells of the human prostate carcinoma cell line PC-3 in athymic nude mice. J Urol 1982, 128:1064–7.PubMedGoogle Scholar
  17. 17.
    Ware JL, Lieberman AP, Webb KS, Vollmer RT. Factors influencing phenotypic diversity of human prostate carcinoma cells metastasizing in athymic nude mice. Exp Cell Biol 1985, 53:163–9.PubMedGoogle Scholar
  18. 18.
    Sherwood E, Ford J, Lee C, Kozlowski J. Therapeutic efficacy of recombinant tumor necrosis factor alpha in an experimental model of human prostatic carcinoma. J Biol Resp Mod 1990, 9:44–52.Google Scholar
  19. 19.
    Shevrin Kukreja D, Ghosh S, Lad LT. Development of skeletal metastasis by human prostate cancer in athymic nude mice. Clin Exp Metastasis 1988, 6:401–9.Google Scholar
  20. 20.
    Shevrin D, Gorny K, Kukreja S. Patterns of metastasis by the human prostate cancer cell line PC-3 in athymic nude mice. Prostate 1989, 15:187–94.PubMedGoogle Scholar
  21. 21.
    Wu TT, Sike RA, Cui Q, Thalmann GN, Kao C, Murphy CF et al. Establishing human prostate cancer cell xenografts in bone: Induction of osteoblastic reaction by prostate specific antigen-producing tumors in athymic and SCID/bg mice using LNCaP and lineage-derived metastatic sublines. Int J Cancer 1998, 77:887–94.PubMedGoogle Scholar
  22. 22.
    Lim DJ, Liu X, Sutkowski DM, Braun EJ, Lee C, Kozlowski JM. Growth of an androgen-sensitive human prostate cancer cell line, LNCaP,, in nude mice. Prostate 1993, 22:109–1.PubMedGoogle Scholar
  23. 23.
    Wang WR, Sordat B, Piguet D, Sordat M. Human colon tumors in nude mice: Implantation site, expression of the invasive phenotype, pp. 239–45. In: Immune-Deficient Animals. 4th Int. Workshop on Immune-Deficient Animals in Experimental Research. Sordat B, ed., Basel: Karger, 1984.Google Scholar
  24. 24.
    Naito S, von Eschenbach AC, Glavazzi R, Fidler IJ. Growth and metastasis of tumor cells isolated from a human renal cell carcinoma implanted into different organs of nude mice. Cancer Res 1986, 46:4109–15.PubMedGoogle Scholar
  25. 25.
    Naito S, von Eschenbach AC, Fidler IJ. Different growth pattern and biologic behavior of human renal cell carcinoma implanted into different organs of nude mice. J Natl Cancer Inst 1987, 78:377–85.PubMedGoogle Scholar
  26. 26.
    Morikawa K, Walker SM, Jessup JM, Fidler IJ. In vivo selection of highly metastatic cells from surgical spcimens of different primary human colon carcinoma implanted into nude mice. Cancer Res 1988, 48:1943–8.PubMedGoogle Scholar
  27. 27.
    Ahlering TE, Dubeau L, Jones PA. A new in vivo model to study invasion and metastasis of human bladder carcinoma. Cancer Res 1987, 47:6660–5.PubMedGoogle Scholar
  28. 28.
    Nakajima M, Morkawa K, Fabra A, Bucana CD, Fidler IJ. Infuence of organ microenvironment on extracellular matrix degradative activity and metastasis of human colon carcinoma cells. J Natl Cancer Inst 1990, 82:1890–8.PubMedGoogle Scholar
  29. 29.
    Price JE, Polyzos A, Zhang RD, Daniels LM. Tumorigenicity and metastasis of human breast carcinoma cell line in nude mice. Cancer Res 1990, 50:717–21.PubMedGoogle Scholar
  30. 30.
    Giavazzi R, Campbell DE, Jessup JM, Cleary K, Fidler IJ. Metastatic behavior of tumor cells isolated from primary and metastatic human colorectal carcinomas implanted into different sites in nude mice. Cancer Res 1986, 46:1928–33.PubMedGoogle Scholar
  31. 31.
    Stephenson RA, Dinney CPN, Gohji K, Ordonez NG, Killion JJ, Fidler IJ. Metastatic model for human prostate cancer using orthotopic implantation in nude mice. J Natl Cancer Inst 1992, 84:951–7.PubMedGoogle Scholar
  32. 32.
    Vieweg J, Heston WDW, Gilboa E, Fair WR. An experimental model simulating local recurrence and pelvic lymph node metastasis following orthotopic induction of prostate cancer. Prostate 1994, 24:291–8.PubMedGoogle Scholar
  33. 33.
    Pettaway CA, Pathak S, Greene G, Ramirez E, Wilson MR, Killion JJ, Fidler IJ. Selection of highly metastatic variants of different human prostatic carcinomas using orthotopic implantation in nude mice. Clin Cancer Res 1996, 2:1627–36.PubMedGoogle Scholar
  34. 34.
    Rembrink K, Romijn JC, van der Kwast TH, Rubben H, Schroder FH. Orthotopic implantation of human prostate cancer cell lines: A clinically relevant animal model for metastatic prostate cancer. Prostate 1997, 31:168–74.PubMedGoogle Scholar
  35. 35.
    Sato N, Gleave ME, Bruchovsky N, Rennie PS, Beraldi E, Sullivan LD. A metastatic and androgen-sensitive human prostate cancer model using intraprostatic inoculation of LNCaP cells in SCID mice. Cancer Res 1997, 57:1584–9.PubMedGoogle Scholar
  36. 36.
    Thalmann GN, Anezinis PE, Chang SM, Zhau HE, Kim EE, Hopwood VL et al. Androgen-independent cancer progression and bone metastasis in the LNCaP model of human cancer. Cancer Res 1994, 54:2577–81.PubMedGoogle Scholar
  37. 37.
    Kusaka N, Nasu Y, Arata R, Saika T, Tsushima T, Kraaij R et al. Transrectal ultrasound for monitoring murine orthotopic prostate tumor. Prostate 2001, 47:118–24.PubMedGoogle Scholar
  38. 38.
    Meyvisch C. Influence of implantation site on formation of metastasis. Cancer Metastasis Rev 1983, 2:295–306.PubMedGoogle Scholar
  39. 39.
    White DC, DeCosse JJ. Experimental arterial dissemination of tumor cells. Cancer 1968, 21:9–15.Google Scholar
  40. 40.
    Stackpole CW. Distant lung-colonizing and lung-metastasizing cell populations in B16 mouse melanoma. Nature 1981, 289:798–800.PubMedGoogle Scholar
  41. 41.
    Fisher B, Fisher ER. Transmigration of lymph nodes by tumor cells. Science 1966, 152:1397–8.PubMedGoogle Scholar
  42. 42.
    Ishibashi T, Yamada H, Harada S, Harada Y, Miyazaki N, Takamoto M, Watanabe K. Distant metastasis facilitated by BCG: Spread of tumor cells injected in the BCG-primed site. Br J Cancer 1980, 41:553–61.PubMedGoogle Scholar
  43. 43.
    Kopf-Maier P. Dying and regeneration of human tumor cells after heterotransplantation to athymic mice. Histol Histopathol 1986, 1:383–90.PubMedGoogle Scholar
  44. 44.
    Kopf-Maier P, Jackel M. Proliferation behavior of xenografted human tumors: A flow cytometric study. Anticancer Res 1988, 8:1355–60.PubMedGoogle Scholar
  45. 45.
    Wilson EL, Gartner M, Campbell JAH, Dowdle EB. Growth and behavior of human melanomas in nude mice.Effect of fibroblasts, pp. 357–61. In: Immuno-Deficient Animals., Sordat B, ed., Karger, 1984.Google Scholar
  46. 46.
    Picard O, Rolland Y, Poupon MF. Fibroblast-dependent tumorigenicity of cells in nude mice: Implication for implantation of metastasis. Cancer Res 1986, 46:3290–4.PubMedGoogle Scholar
  47. 47.
    Horgan K, Jones DL, Mansel RE. Mitogenicity of human fibroblasts in vivo for human breast cancer cells. Br J Surg 1987, 74:227–9.PubMedGoogle Scholar
  48. 48.
    Fridman R, Giaccone G, Kanemoto T, Martin GR, Gazdar AF, Mulshine JL. Reconstituted basement membrane (matrigel) and laminin can enhance the tumorigenicity and the drug resistance of small cell lung cancer cell lines. Proc Natl Acad Sci USA 1990, 87:6689–702.Google Scholar
  49. 49.
    Pretlow TG, Delmoro CM, Dilley GG, Spadafora CG, Pretlow TP. Transplantation of human prostate carcinoma into nude mice in matrigel. Cancer Res 1991, 51:3814–7.PubMedGoogle Scholar
  50. 50.
    Fridman R, Kibbey MC, Royce LS, Zain M, Sweeney TM, Jicha DL et al. Enhanced tumor growth of both primary and established human and murine tumor cells in athymic mice after coinjection with matrigel. J Natl Cancer Inst 1991, 83:769–4.PubMedGoogle Scholar
  51. 51.
    Noel A, Borcy V, Bracke M, Gilles C, Bernard J, Birembaut P et al. Heterotransplantation of primary and established human tumor cells in nude mice. Anticancer Res 1995, 15:1–8.PubMedGoogle Scholar
  52. 52.
    Kleinman HK. Basement membrane complexes with biological activity. Biochemistry 1986, 25:312–8.PubMedGoogle Scholar
  53. 53.
    Liotta LA, Steeg PS, Stetler-Stevenson WG. Metastasis and angiogenesis: An imbalance of positive and negative regulation. Cancer 1991, 64:327–6.Google Scholar
  54. 54.
    Passaniti A, Isaacs JT, Haney JA, Adler SW, Cujdik TJ, Long PV, Kleinman HK. Stimulation of human prostate carcinoma tumor growh in athymic mice and control of migration in culture by extracellular matrix. Int J Cancer 1992, 51:318–24.PubMedGoogle Scholar
  55. 55.
    Fu X, Besterman JM, Monosov A, Hoffman RM. Models of human metastatic colon cancer in nude mice orthotopically constructed by using histologically-intact patient specimens. Proc Natl Acad Sci USA 1991, 88:9345–9.PubMedGoogle Scholar
  56. 56.
    Fu X, Herrera H, Kubota T, Hoffman RM. Extensive liver metastasis from human colon cancer in nude and scid mice after orthotopic onplantation of histologically-intact human colon carcinoma tissue. Anticancer Res 1992, 12:1395–8.PubMedGoogle Scholar
  57. 57.
    Fu X, Theodorescu D, Kerbel RS, Hoffman RM. Extensive multi-organ metastasis following orthotopic onplantation of histologically-intact human bladder carcinoma tissue in nude mice. Int J Cancer 1991, 49:938–9.PubMedGoogle Scholar
  58. 58.
    Fu X, Hoffman RM. Human RT-4 bladder carcinoma is highly metastatic in nude mice, comparable to rash-transformed RT-4 when orthotopically onplanted as histologically-intact tissue. Int J Cancer 1992, 51:989–1.PubMedGoogle Scholar
  59. 59.
    Wang X, Fu X, Hoffman RM. A new patient-like metastatic model of human lung cancer constructed orthotopically with intact tissue via thoracotomy in immunodeficient mice. Int J Cancer 1992, 51:992–5.PubMedGoogle Scholar
  60. 60.
    Wang X, Fu X, Hoffman RM. A patient-like metastasizing model of human lung adenocarcinoma constructed via thoracotomy in nude mice. Anticancer Res 1992, 12:1399–402.PubMedGoogle Scholar
  61. 61.
    Wang X, Fu X, Kubota T, Hoffman RM. A new patient-like metastatic model of human small-cell lung cancer constructed orthotopically with intact tissue via thoracotomy in nude mice. Anticancer Res 1992, 12:1403–6.PubMedGoogle Scholar
  62. 62.
    Kuo T-H, Kubota T, Watanabe M, Furukawa T, Kase S, Tanino H et al. Orthotopic reconstitution of human small-cell lung carcinoma after intravenous transplantation in SCID mice. Anticancer Res 1992, 12:1407–0.PubMedGoogle Scholar
  63. 63.
    Fu X, Guadagni F, Hoffman RM. A metastatic nude-mouse model of human pancreatic cancer constructed orthotopically from histologically intact patient specimens. Proc Natl Acad Sci USA 1992, 89:5645–9.PubMedGoogle Scholar
  64. 64.
    Furukawa T, Fu X, Kubota T, Watanabe M, Kitajima M, Hoffman RM. Nude mouse metastatic models of human stomach cancer constructed using orthotopic implantation of histologically intact tissue. Cancer Res 1993, 53:1204–8.PubMedGoogle Scholar
  65. 65.
    An Z, Jiang P, Wang X, Moossa AR, Hoffman RM. Development of a high metastatic orthotopic model of human renal cell carcinoma in nude mice: Benefits of fragment implantation compared to cell-suspension injection. Clin Exp Metastasis 1999, 17:265–70.PubMedGoogle Scholar
  66. 66.
    Fu X, Le P, Hoffman RM. A metastatic orthotopic-transplant nude-mouse model of human patient breast cancer. Anticancer Res 1993, 13:901–4.PubMedGoogle Scholar
  67. 67.
    Fu X, Hoffman RM. Human ovarian carcinoma metastatic models constructed in nude mice by orthotopic transplantation of histologically-intact patient specimens. Anticancer Res 1993, 13:283–6.PubMedGoogle Scholar
  68. 68.
    Chishima T, Miyagi Y, Wang X, Tan Y, Shimada H, Moossa AR, Hoffman RM. Visualization of the metastatic process by green fluorescent protein expression. Anticancer Res 1997, 17:2377–84.PubMedGoogle Scholar
  69. 69.
    Chishima T, Miyagi Y, Wang X, Baranov E, Tan Y, Shimada H et al. Metastatic patterns of lung cancer visualized live and in process by green fluorescence protein expression. Clin Exp Metastasis 1997, 15:547–2.PubMedGoogle Scholar
  70. 70.
    Chishima T, Miyagi Y, Li L, Tan Y, Baranov E, Yang M et al. Use of histoculture and green fluorescent protein to visualize tumor cell host interaction. In Vitro Cell Dev Biol Animal 1997, 33:745–7.Google Scholar
  71. 71.
    Chishima T, Yang M, Miyagi Y, Li L, Tan Y, Baranov E et al. Governing step of metastasis visualized in vitro. Proc Natl Acad Sci USA 1997, 94:11573–6.PubMedGoogle Scholar
  72. 72.
    Yang M, Hasegawa S, Jiang P, Wang X, Tan Y, Chishima T et al. Widespread skeletal metastatic potential of human lung cancer revealed by green fluorescent protein expression. Cancer Res 1998, 58:4217–21.PubMedGoogle Scholar
  73. 73.
    Dolman CS, Mueller BM, Lode HN, Xiang R, Gillies SD, Reisfeld RA. Suppression of human prostate carcinoma metastases in severe combined immunodeficient mice by interleukin 2 immunocytokine therapy. Clin Cancer Res 1998, 4:2551–7.PubMedGoogle Scholar
  74. 74.
    Yang M, Jiang P, Sun FX, Hasegawa S, Baranov E, Chishima T et al. A fluorescent orthotopic bone metastasis model of human prostate cancer. Cancer Res 1999, 59:781–6.PubMedGoogle Scholar
  75. 75.
    Fidler IJ. Critical factors in the biology of human cancer metastasis: Twenty-eigth G.H.A. clows memorial award lecture. Cancer Res 1990, 50:6130–8.PubMedGoogle Scholar
  76. 76.
    Poste G, Fidler IJ. The pathogenesis of cancer metastasis. Nature 1980, 283:139–45.PubMedGoogle Scholar
  77. 77.
    Feldman M, Eisenbach L. What makes a tumor cell metastatic. Sci Am 1988, 259:60–5, 68, 85.Google Scholar
  78. 78.
    Waters DJ, Janovitz EB, Chan TCK. Spontaneous metastasis of PC-3 cells in athymic mice after implantaion in orthotopic or ectopic microenvironments. Prostate 1995, 26:227–34.PubMedGoogle Scholar
  79. 79.
    Ozen M, Multani AS, Kuniyasu H, Chung LW, von Eschenbach AC, Pathak S. Specific histologic and cytogenetic evidence for in vivo malignant transformation of murine host cells by three human prostate cancer cell lines. Oncol Res 1997, 9(8):433–8.PubMedGoogle Scholar
  80. 80.
    Hall SJ, Thompson TC. Spontaneous but not experimental metastatic activities differentiate primary tumor-derived vs metastasis-derived mouse prostate cancer cell lines. Clin Exp Metastasis 1997, 15:630–8.PubMedGoogle Scholar
  81. 81.
    Chang XH, Fu YW, Na WL, Wang J, Sun H, Cai L. Improved metastatic animal model of human prostate carcinoma using surgical orthotopic implantation (SOI). Anticancer Res 1999, 19(5B):4199–202.PubMedGoogle Scholar
  82. 82.
    Wang X, An Z, Geller J, Hoffman RM. High malignancy orthotopic nude mouse model of human prostate cancer LNCaP. Prostate 1999, 39:182–6.PubMedGoogle Scholar
  83. 83.
    Mundy GR. Mechanisms of bone metastasis. Cancer 1997, 80:1546–56.PubMedGoogle Scholar
  84. 84.
    Maeda H, Segawa T, Kamoto T, Yoshida H, Kakizuka A, Ogawa O, Kakehi Y. Rapid detection of candidate metastatic foci in the orthotopic inoculation model of androgen-sensitive prostate cancer cells introduced with green fluorescent protein. Prostate 2000, 45:335–40.PubMedGoogle Scholar
  85. 85.
    Patel S, Turner PR, Stubberfield C, Barry E, Rohlff CR, Stamps A et al. Hyaluronidase gene profiling and role of hyal-1 overexpression in an orthotopic model of prostate cancer. Int J Cancer 2002, 97:416–24.PubMedGoogle Scholar
  86. 86.
    Cao G, Su J, Lu W, Zhang F, Zhao G, Marteralli D, Dong Z. Adenovirus-mediated interferon-beta gene therapy suppresses growth and metastasis of human prostate cancer in nude mice. Cancer Gene Ther 2001, 8:497–505.PubMedGoogle Scholar
  87. 87.
    Chu LW, Pettaway CA, Liang JC. Genetic abnormalities specifically associated with varying metastatic potential of prostate cancer cell lines as detected by comparative genomic hybridization. Cancer Genet Cytogenet 2001, 127:161–7.PubMedGoogle Scholar
  88. 88.
    Bex A, Wullich B, Endris V, Otto T, Rembrink K, Stockle M, Rubben H. Comparison of the malignant phenotype and genotype of the human androgen-independent cell line DU-145 and a subline derived from metastasis after orthotopic implantation in nude mice. Cancer Genet Cytogenet 2001, 124:98–104.PubMedGoogle Scholar
  89. 89.
    Timár J, Rásó E, Döme B, Li L, Grignon D, Nie D et al. Expression, subcellular localization and putative function of platelet-type 12-lipoxygenase in human prostate cancer cell lines of different metastatic potential. Int J Cancer 2000, 87:37–43.PubMedGoogle Scholar
  90. 90.
    Inoue K, Slaton JW, Eve BY, Kim SJ, Perrotte P, Balbay MD et al. Interleukin 8 expression regulates tumorigenicity, metastases in androgen-independent prostate cancer. Clin Cancer Res 2000, 6:2104–19.PubMedGoogle Scholar
  91. 91.
    Stearns ME, Wang M. Antimestatic and antitumor activities of interleukin 10 in transfected human prostate PC-3 ML clones: Orthotopic growth in severe combined immunodeficient mice. Clin Cancer Res 1998, 4:2257–63.PubMedGoogle Scholar
  92. 92.
    Stearns ME, Garcia FU, Fudge K, Rhim J, Wang M. Role of interleukin 10 and transforming growth factor BETA1 in the angiogenesis and metastasis of human prostate primary tumor lines from orthotopic implants in severe combined immunodeficiency mice. Clin Cancer Res 1999, 5:711–20.PubMedGoogle Scholar
  93. 93.
    Trikha M, Raso E, Cai Y, Fazakas Z, Paku S, Porter AT et al. Role of alphaii(b)BETA3 integrin in prostate cancer metastasis. Prostate 1998, 35:185–92.PubMedGoogle Scholar
  94. 94.
    Marengo SR, Sikes RA, Anezinis P, Chang SM, Chung LW. Metastasis induced by overexpression of P185NEU-T after orthotopic injection into a prostatic epithelial cell line (nbe). Mol Carcinog 1997, 19:165–75.PubMedGoogle Scholar
  95. 95.
    Greene GF, Kitadai Y, Pettaway CA, von Eschenbach AC, Bucana CD, Fidler IJ. Correlation of metastasis-related gene expression with metastatic potential in human prostate carcinoma cells implanted in nude mice using an in situ messenger RNA hybridization technique. Am J Pathol 1997, 150:1571–82.PubMedGoogle Scholar
  96. 96.
    Olson KA, Byers HR, Key ME, Fett JW. Prevention of human prostate tumor metastasis in athymic mice by antisense targeting of human angiogenin. Clin Cancer Res 2001, 7:3598–605.PubMedGoogle Scholar
  97. 97.
    Dong Z, Greene G, Pettaway C, Dinney CP, Eue I, Lu W et al. Suppression of angiogenesis, tumorigenicity, and metastasis by human prostate cancer cells engineered to produce interferon-beta. Cancer Res 1999, 59:872–9.PubMedGoogle Scholar
  98. 98.
    Nasu Y, Bangma CH, Hull GW, Lee HM, Hu J, Wang J et al. Adenovirus-mediated interleukin-12 gene therapy for prostate cancer: Suppression of orthotopic tumor growth and pre-established lung metastases in an orthotopic model. Gene Ther 1999, 6:338–49.PubMedGoogle Scholar
  99. 99.
    Hull GW, Mccurdy MA, Nasu Y, Bangma CH, Yang G, Shimura S et al. Prostate cancer gene therapy: Comparison of adenovirus-mediated expression of interleukin 12 with interleukin 12 plus B7-1 for in situ gene therapy and gene-modified, cell-based vaccines. Clin Cancer Res 2000, 6:4101–9.PubMedGoogle Scholar
  100. 100.
    Eastham JA, Grafton W, Martin CM, Williams BJ. Suppression of primary tumor growth and the progression to metastasis with P53 adenovirus in human prostate cancer. J Urol 2000, 164(3 Pt 1):814–9.PubMedGoogle Scholar
  101. 101.
    Hall SJ, Mutchnik SE, Chen SH, Woo SL, Thompson TC. Adenovirus-mediated herpes simplex virus thymidine kinase gene and ganciclovir therapy leads to systemic activity against spontaneous and induced metastasis in an orthotopic mouse model of prostate cancer. Int J Cancer 1997, 70:183–7.PubMedGoogle Scholar
  102. 102.
    Hall SJ, Sanford MA, Atkinson G, Chen SH. Induction of potent antitumor natural killer cell activity by herpes simplex virus-thymidine kinase and ganciclovir therapy in an orthotopic mouse model of prostate cancer. Cancer Res 1998, 58:3221–5.PubMedGoogle Scholar
  103. 103.
    Maeda H, Hori S, Nishitoh H, Ichijo H, Ogawa O, Kakehi Y, Kakizuka A. Tumor growth inhibition by arsenic trioxide (AS2O3) in the orthotopic metastasis model of androgen-independent prostate cancer. Cancer Res 2001, 61:5432–40.PubMedGoogle Scholar
  104. 104.
    Tahir SA, Yang G, Ebara S, Timme TL, Satoh T, Li L et al. Secreted caveolin-1 stimulates cell survival/clonal growth and contributes to metastasis in androgen-insensitive prostate cancer. Cancer Res 2001, 61:3882–5.PubMedGoogle Scholar
  105. 105.
    Saffran DC, Raitano AB, Hubert RS, Witte ON, Reiter RE, Jakobovits A. Anti-PSCA mAbs inhibit tumor growth and metastasis formation and prolong the survival of mice bearing human prostate cancer xenografts. Proc Natl Acad Sci USA 2001, 98:2658–63.PubMedGoogle Scholar
  106. 106.
    Anidjar M, Villette JM, Devauchelle P, Delisle F, Cotard JP, Billotey C et al. In vivo model mimicking natural history of dog prostate cancer using DPC-1, a new canine prostate carcinoma cell line. Prostate 2001, 46:2–10.PubMedGoogle Scholar
  107. 107.
    Yang M, Baranov E, Jiang P, Sun F-X, Li X-M, Li L et al. Whole-body optical imaging of green fluorescent protein-expressing tumors and metastases. Proc Natl Acad Sci USA 2000, 97:1206–1.PubMedGoogle Scholar
  108. 108.
    Yang M, Baranov E, Li X-M, Wang J-W, Jiang P, Li L et al. Whole-ody and intravital optical imaging of angiogenesis in orthotopically implanted tumors. Proc Natl Acad Sci USA 2001, 98:2616–1.PubMedGoogle Scholar
  109. 109.
    Yang, Baranov ME, Moossa AR, Penman S, Hoffman RM. Visualizing gene expression by whole-body fluorescence imaging. Proc Natl Acad Sci USA 2000, 97:12278–82.PubMedGoogle Scholar
  110. 110.
    Yang M, Baranov E, Wang J-W, Jiang P, Wang X, Sun F-X et al. Direct external imaging of nascent cancer, tumor progression, angiogenesis, and metastasis on internal organs in the fluorescent orthotopic model. Proc Natl Acad Sci USA 2002, 99:3824–9.PubMedGoogle Scholar
  111. 111.
    Hoffman RM. Orthotopic metastatic mouse models for anticancer drug discovery and evaluation: A bridge to the clinic. Invest New Drugs 1999, 17:343–59.Google Scholar
  112. 112.
    Knox JD, Mack CF, Powell WC, Bowden GT, Nagle RB. Prostate tumor cell invasion: A comparison of orthotopic and ectopic models. Invasion Metastasis 1993, 13:325–1.PubMedGoogle Scholar
  113. 113.
    Gupta S, Hastek K, Ahmad N, Lewin JS, Mukhtar H. Inhibhtion of prostate carcinogenesis in TRAMP mice by oral infusion of green tea polyphenols. Proc Natl Acad Sci USA 2001, 98:10350–55.PubMedGoogle Scholar

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© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Robert M. Hoffman
    • 1
  1. 1.Department of SurgeryUCSD Medical CenterSan DiegoUSA

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