Abstract
A valid experimental model system reflects the system under study and is reproducible. Model systems of prostate cancer that accurately reflect the different disease stages are necessary to ensure a proper experimental design aimed at increasing our understanding of the biology of the disease and such models are essential tools to accelerate development of new therapies for prostate cancer. Until recently, a limited number of experimental systems were available and more suitable models derived from human specimens have only recently been developed and become available for use. In addition, transgenic techniques have also permitted the development of unique mouse models. The difficulty in establishing model systems may reflect the complex requirements necessary for cancer progression and should lead us to interpret results from model systems with caution. It is unlikely that a single model system that faithfully reflects the whole process of cancer development and progression will be developed. However, thoughtful use of the available model systems will permit the study of a significant portion of prostate cancer progression. In this review we summarize the properties of the prostate cancer model systems in use and defined their utility and limitations. This review will guide the investigator seeking models with which to test specific hypotheses pertaining to prostate cancer.
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Landis SH, Tong T, Murray T, Bolden S, Wingo PA: Cancer statistics. CA Cancer J Clin 48: 6-30, 1998
Dunning WF: Prostate cancer in the rat. J Natl Cancer Inst Monogr 12: 351-369, 1963
Lubaroff DM, Canfield L, Reynolds CW: The Dunning tumors. Prog Clin Biol Res 37: 243-263, 1980
Isaacs JT, Weissman RM, Coffey DS, Scott WW: Concepts in prostatic cancer biology: Dunning R. 3327 H, HI, and AT tumors. Prog Clin Biol Res 37: 311-323, 1980
Isaacs JT, Yu GW, Coffey DS: The characterization of a newly identified, highly metastatic variety of Dunning R 3327 rat prostatic adenocarcinoma system: the MAT LyLu tumor. Invest Urol 19(1): 20-23, 1981
Quarmby VE, Beckman WC Jr, Cooke DB, Lubahn DB, Joseph DR, Wilson EM, French FS: Expression and localization of androgen receptor in the R. 3327 Dunning rat prostatic adenocarcinoma. Cancer Res 50(3): 735-739, 1990
Isaacs JT, Isaacs WB, Feitz WF, 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 9(3): 261-281, 1986
Isaacs JT: The aging ACI/Seg versus Copenhagen male rat as a model system for the study of prostatic carcinogenesis. Cancer Res 44(12 Pt 1): 5785-5796, 1984
Pugh TD, Chang C, Uemura H, Weindruch R: Prostatic localization of spontaneous early invasive carcinoma in Lobund Wistar rats. Cancer Res 54(22): 5766-5770, 1994
Lucia MS, Bostwick DG, Bosland M, Cockett ATK, Knapp DW, Leav I, Pollard M, Rinker Schaeffer C, Shirai T, Watkins BA: Workgroup 1: Rodent models of prostate cancer. Prostate 36(1): 49-55, 1998
Camps JL, Chang SM, Hsu TC, Freeman MR, Hong SJ, Zhau HE, von Eschenbach AC, Chung LW: Fibroblast-mediated acceleration of human epithelial tumor growth in vivo. Proc Natl Acad Sci USA 87(1): 75-79, 1990
Chang SM, Chung LW: Interaction between prostatic fibroblast and epithelial cells in culture: role of androgen. Endocrinology 125(5): 2719-2727, 1989
Rowley DR, Characterization of a fetal urogenital sinus mesenchymal cell line U4F: secretion of a negative growth regulatory activity. In vitroCell Dev Biol 28A(1): 29-38, 1992
Gerdes MJ, Dang TD, Lu B, Larsen M, McBride L, Rowley DR, Androgen-regulated proliferation and gene transcription in a prostate smooth muscle cell line (PS-1). Endocrinology 137(3): 864-872, 1996
Waters DJ, Sakr WA, Hayden DW, Lang CM, McKinney L, Murphy GP, Radinsky R, Ramoner R, Richardson RC, Tindall DJ: Workgroup 4: spontaneous prostate carcinoma in dogs and nonhuman primates. Prostate 36(1): 64-67, 1998
Waters DJ, Hayden DW, Bell FW, Klausner JS, Qian J, Bostwick DG: Prostatic intraepithelial neoplasia in dogs with spontaneous prostate cancer. Prostate 30(2): 92-97, 1997
Thompson TC, Kadmon D, Timme TL, Merz VW, Egawa S, Krebs T, Scardino PT, Park SH: Experimental oncogene induced prostate cancer. Cancer Surv 11: 55-71, 1991
Thompson TC, Truong LD, Timme TL, Kadmon D, McCune BK, Flanders KC, Scardino PT, Park SH: Transgenic models for the study of prostate cancer. Cancer 71(3): 1165-1171, 1993
Thompson TC, Park SH, Timme TL, Ren C, Eastham JA, Donehower LA, Bradley A, Kadmon D, Yang G: Loss of p53 function leads to metastasis in rasCmyc initiated mouse prostate cancer. Oncogene 10(5): 869-879, 1995
Eastham JA, Stapleton AMF, Gousse AE, Timme TL, Yang G, Slawin KM, Wheeler TM, Scardino PT, Thompson TC: Association of p53 mutations with metastatic prostate cancer. Clin Cancer Res 1: 1111-1118, 1995
Navone NM, Troncoso P, Pisters LL, Goodrow TL, Palmer JL, Nichols WW, von Eschenbach AC, Conti CJ: p53 protein accumulation and gene mutation in the progression of human prostate carcinoma. J Natl Cancer Inst 85: 1657-1669, 1993
Navone NM, LaBate ME, Troncoso P, Pisters LL, Conti CJ, von Eschenbach AC, Logothetis CJ: p53 mutations in prostate cancer bone metastases suggest that selected p53 mutants in the primary site define foci with metastatic potential. J Urology 161(1): 304-308, 1999
Nasu Y, Timme TL, Yang G, Bangma CH, Li L, Ren C, Park SH, DeLeon M, Wang J, Thompson TC: Suppression of caveolin expression induces androgen sensitivity in metastatic androgen insensitive mouse prostate cancer cells. Nat Med 4(9): 1062-1064, 1998
Greenberg NM, DeMayo F, Finegold MJ, Medina D, Tilley WD, Aspinall JO, Cunha GR, Donjacour AA, Matusik RJ, Rosen JM: Prostate cancer in a transgenic mouse. Proc Nati Acad Sci USA 92: 3439-3443, 1995
Kasper S, Sheppard PC, Yan Y, Pettigrew N, Borowsky AD, Prins GS, Dodd JG, Duckworth, ML, Matusik RJ: Development, progression, and androgen dependence of prostate tumors in probasin large T antigen transgenic mice: a model for cancer. Lab Invest 78(6): i-xv, 1998
Cleutjens KB, van der Korput HA, Ehren van Eekelen CC, Sikes RA, Fasciana C, Chung LW, Trapman J, A 6-kb promoter fragment mimics in transgenic mice the prostate specific and androgen regulated expression of the endogenous prostate specific antigen gene in humans. Mol Endocrinol 11(9): 1256-1265, 1997
Maroulakou IG, AnverM, Garrett L, Green JE: Prostate and mammary adenocarcinoma in transgenic mice carrying a rat C3(1) simian virus 40 large tumor antigen fusion gene. Proc Natl Acad Sci USA 91(23): 11236-11240, 1994
Gingrich JR, Barrios RJ, Kattan MW, Nahm HS, Finegold MJ, Greenberg NM: Androgen independent prostate cancer progression in the TRAMP model. Cancer Res 57(21): 4687-4691, 1997
Stapleton AMF, Timme TL, Gousse AE, Li QF, Tobon AA, Kattan MW, Slawin KM, Wheeler TM, Scardino TL, Thompson TC: Primary human prostate cancer cells harboring p53 mutations are clonally expanded in metastases. Clin Cancer Res 3: 1389-1392, 1997.
Heidenberg HB, Bauer JJ, McLeod DG, Moul JW, Srivastava S: The role of the p53 tumor suppressor gene in prostate cancer: a possible biomarker? Urology 48: 971-979, 1996
Green JE, Greenberg NM, Ashendel CL, Barrett JC, Boone C, Getzenberg RH, Henkin J, Matusik R, Janus TJ, Scher HI: Workgroup 3: transgenic and reconstitution models of prostate cancer. Prostate 36(1): 59-63, 1998
Ellis WJ, Vassella RL, Buhler KR, Bladou F, True LD, Bigler SA, Curtis D, Lange PH: Characterization of a novel androgen sensitive, prostate specific antigen producing prostate carcinoma xenograft: LuCaP 23. Clin Cancer Res 2: 1039-1048, 1996
Gittes RF: Carcinoma of the prostate. N EngI J Med 324: 236-245, 1991
Catalona WJ: Management of cancer of the prostate. N Engl J Med 331: 996-1004, 1994
Scher HI, Steineck G, Kelly WK: Hormone. refractory (D3) prostate cancer: Refining the concept. Urology 46: 142-148, 1995.
Peehl DM: Culture of human prostatic epithelial cells. In: Culture of Epithelial Cells, Freshney RA (ed) Wiley-Liss, New York, pp 159-180, 1992
Chaproniere DM, McKeehan WL: Serial culture of single adult human prostatic epithelial cells in serum-free medium containing low calcium and a new growth factor from bovine brain. Cancer Res 46: 819-824, 1986
Konig JJ, van Dongen JW, Schroder FH: Preferential loss of abnormal prostate carcinoma cells by collagenase treatment. Cytometry 14: 805-810, 1993
Konig JJ, Teubel W, van Dongen JW, Hagemeijer A, Romijn JC, Schroder FH: Tissue culture loss of aneuploid cells from carcinoma of the prostate. Genes Chrom Cancer 8: 22-27, 1993
Jones E, Zhu XL, Rohr LR, Stephenson RA, Brothman AR: Aneusomy of chromosomes 7 and 17 detected by FISH in prostate cancer and the effect of selection in vitro. Genes Chrom Cancer 11: 163-170, 1994.
Horoszewicz JS, Leong SS, Kawinski E, Karr JP, Rosenthal H, Chu TM, Mirand EA, Murphy GP: LNCaP model of human prostatic carcinoma. Cancer Res 43: 1809-1818, 1983
Passaniti A, Isaacs JT, Haney JA, Adler SW, Cujdik TJ, Long PV, Kleinman HK: Stimulation of human prostatic carcinoma tumor growth in athymic mice and control of migration in culture by extracellular matrix. Int J Cancer 51: 318-324, 1992
Gleave M, Hsieh JT, Gao C, von Eschenbach AC, Chung LWK: Acceleration of human prostate cancer growth in vivoby factors produced by prostate and bone fibroblasts. Cancer Res 51: 3753-3761, 1991
Veldscholte J, Ris Staplers C, Kuiper GGJM, Jenster G, Berrevoets C, Classen E, van Fooij HCJ, Trapman J, Brinkman AO, Muler E: A mutation in the ligand binding domain of the androgen receptor of human LNCaP cells affects steroid binding characteristics and response to anti-androgens. Biochem Biophys Res Commun 173: 534-540, 1990
Wilding G, Chen M, Gelmann E: Aberrant response in vitroof hormone responsive prostate cancer cells to anti-androgens. Prostate 14: 103-115, 1989
Kokontis J, Kiyoshi, Hiipakka RA, Kiao S: Expression and function of normal and LNCaP androgen receptors in androgen insensitive human prostatic cancer cells. Altered hormone and antihormone specificity in gene transactivation. Receptor 1: 271-270, 1991
Taplin ME, Bubley GJ, Shuster TD, Frantz ME, Spooner AE, Ogata OK, Keer HN, Balk SP: Mutation of the androgen receptor gene in metastatic androgen independent prostate cancer. N Engl J Med 332: 1393-1398, 1995
Koivisto P, Kolmer M, Visakorpi T, Kallioniemi OP: Androgen receptor gene and hormonal therapy failure of prostate cancer. Am J Pathol 152: 1-9, 1998
Tilley WD, Buchanan G, Hickey TE, Bentel JM: Mutations in the androgen receptor gene are associated with progression of human prostate cancer to androgen independence. Clin Cancer Res 2(2): 277-285, 1996
Peterziel H, Culig Z, Stober J, Hobisch A, Radmayr C, Bartsch G, KIocker H, Cato ACB: Mutant androgen receptors in prostatic tumors distinguish between amino acid sequence requirements for transactivation and ligand binding. Int J Cancer 63(4): 544-550, 1995
Hobisch A, Culig Z, Radmayr C, Bartsch G, Klocker H, Hittmair A: Distant metastases from prostatic carcinoma express androgen receptor protein. Cancer Res 55(14): 3068-3072, 1995
Koivisto P, Hyytinen E, Palmberg C, Tammela T, Visakorpi T, Isola J, Kallioniemi OP: Analysis of genetic changes underlying local recurrence of prostate carcinoma during androgen deprivation therapy. Am J Pathol 147 (6): 1608-1614, 1995
Cunha GR: The role of androgens in the epitheliomesenchymal interactions involved in prostatic morphogenesis in embryonic mice. Anat Rec 175(1): 87-96, 1973
Cunha GR, Chung LW: Stromal-epithelial interactions - I. Induction of prostatic phenotype in urothelium of testicular feminized (Tfm/y) mice. J Steroid Biochem 14(12): 1317-1324, 1981
Wu HC, Hsieh JT, Gleave ME, Brown NM, Pathak S, Chung LW: Derivation of androgen independent human LNCaP prostatic cancer cell sublines: role of bone stromal cells. Int J Cancer 57(3): 406-412, 1994
Wu TT, Sikes RA, Cui Q, Thalmann GN, Kao C, Murphy CF, Yang H, Zhau HE, Balian G, Chung LW: 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 77(6): 887-894, 1998
Thalmann GN, Anezinis PE, Chang SM, Zhau HE, Kim EE, Hopwood VL, Pathak S, von Eschenbach, AC, Chung LW: Androgen-independent cancer progression and bone metastasis in the LNCaP model of human prostate cancer. Cancer Res 54(10): 2577-2581, 1994
Pettaway CA, Pathak S, Greene G, Tamirez E, Wilson MR, Killion JJ, Fidler IJ: Selection of highly metastatic variants of different human prostate carcinomas using orthotopic implantation in nude mice. Clin Cancer Res 2: 1627-1636, 1996
Stephenson RA, Dinney CP, Gohji K, Ordonez NG, Killion JJ, Fidler JJ: Metastatic model for human prostate cancer using orthotopic implantation in nude mice. J Natl Cancer Inst 84(12): 951-957, 1992
Chen ME, Lin SH, Chung LW, Sikes RA: Isolation and characterization of PAGE 1 and GAGE 7. New genes expressed in the LNCaP prostate cancer progression model that share homology with melanoma associated antigens. J Biol Chem 273(28): 17618-17625, 1998
McConkey DJ, Greene G, Pettaway CA: Apoptosis resistance increases with metastatic potential in cells of the human LNCap prostate carcinoma line. Cancer Res 56(24): 5594-5599, 1996
Navone NM, Olive M, Ozen M, Davis R, Troncoso P, Tu S-M, Johnston D, Pollack A, Pathak S, von Eschenbach AC, Logothetis CJ: Establishment of two human prostate cancer cell lines derived from a single bone metastasis. Clin Cancer Res 3: 2493-2500, 1997
Kaighn ME, N Shankar, Ohnuki Y, Lechner F, Jones LW: Establishment and characterization of a human prostatic carcinoma cell line (PC. 3). Investigative Urol 17: 16-23, 1979
Stone KR, Mickey DD, Wunderli H, Mickey GH, Paulson DF: Isolation of a human prostate carcinoma cell line (DU145). Intl J Cancer 21: 274-281, 1978
Iizumi T, Yazaki T, Kanoh S, Kondo I, Koiso K: Establishment of a new prostatic carcinoma cell line (TSU. Pr1). J Urol 137(6): 1304-1306, 1987
Zhau HYE, Chang S-M, Chen B-Q, Wang Y, Zhang H, Kao C, Sang QA, Pathak SJ, Chang LWK: Androgen-repressed phenotype in human prostate cancer. Proc Natl Acad Sci USA 93: 15152-15157, 1996
Hoehn W, Schroeder FH, Reimann JF, Joebsis AC, Hermanek P: Human prostatic adenocarcinoma: some characteristics of serially transplantable line in nude mice (PC 82). Prostate 1(1): 95-100, 1980
Pretlow TG, Wolman SR, Micale MA, Pelley RJ, Kursh ED, Resnick MI, Bodner DR, Jacobberger JW, Delmoro CM, Giaconia JM, et al.: Xenografts of primary human prostatic carcinoma. J Natl Cancer Inst 85(5): 394-398, 1993
Tan J, Sharief Y, Hamil KG, Gregory CW, Zang DY, Sar M, Gumerlock PH, deVere White RW, Pretlow TG, Harris SE, Wilson EM, Mohler JL, French FS: Dehydroepiandrosterone activates mutant androgen receptors expressed in the androgen dependent human prostate cancer xenograft CWR22 and LNCaP cells. Mol Endocrinol 11(4): 450-459, 1997
Nagabhushan M, Miller CM, Pretlow TP, Giaconia JM, Edgehouse NL, Schwartz S, Kung HJ, de Vere White RW, Gumerlock PH, Resnick MI, Amini SB, Pretlow TG: CWR22: the first human prostate cancer xenograft with strongly androgen-dependent and relapsed strains both in vivoand in soft agar. Cancer Res 56(13): 3042-3046, 1996
vanWeerden WM, de Ridder CM, Verdaasdonk CL, Romijn JC, van der Kwast TH, Schroder FH, van Steenbrugge GJ: Development of seven new human prostate tumor xenograft models and their histopathological characterization. Am J Pathol 149(3): 1055-1062, 1996
Klein KA, Reiter RE, Redula J, Moradi H, Zhu XL, Brothman AR, Lamb DJ, Marcelli M, Belidegrun A, Witte ON, Sawyers CL: Progression of metastatic human prostate cancer to androgen independence in immunodeficient SCID mice. Nature Med 3(4): 402-408, 1997
Olumi AF, Dazin P, Tlsty TD: A novel coculture technique demonstrates that normal human prostatic fibroblasts contribute to tumor formation of LNCap cells by retarding cell death. Cancer Res 58(20): 4525-4530, 1998
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Navone, N.M., Logothetis, C.J., von Eschenbach, A.C. et al. Model Systems of Prostate Cancer: Uses and Limitations. Cancer Metastasis Rev 17, 361–371 (1998). https://doi.org/10.1023/A:1006165017279
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DOI: https://doi.org/10.1023/A:1006165017279