Skip to main content
Log in

Culturing precision-cut human prostate slices as an in vitro model of prostate pathobiology

  • Published:
Cell Biology and Toxicology Aims and scope Submit manuscript

Abstract

Due to the complex morphology of the prostate, it was hypothesized that precision-cut tissue slices from human prostate would provide a unique in vitro model. Precision-cut slices were generated from zones of human prostate and their viability was assessed under conditions of different media for up to 120 h. Slices were also exposed to several concentrations of CdCl2, which was used as a model toxicant. Maintenance of both stromal and epithelial cells was noted; however, there was a gradual loss of luminal epithelial cells when the medium was not supplemented with dihydrotestosterone (DHT). Minimal leakage of lactate dehydrogenase occurred throughout the incubation. Prostate-specific antigen (PSA) was detected in the medium at all time points, although the rates of secretion fell over time. There was a loss of PSA-positive cells when the medium was not supplemented with DHT, consistent with a loss of luminal cells, whereas PSA-positive cells were maintained in the DHT-supplemented media. A proliferation of basal cells was observed in the presence of media containing 10% fetal bovine serum. Exposure of slices to CdCl2 demonstrated a dose-response effect ranging from proliferation to complete cellular necrosis. Given the retention of stromal-epithelial interactions and the use of acquired human tissue, prostate slices represent a unique in vitro model for investigating human prostate pathobiology.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Achanzar WE, Bhalchandra AD, Liu J, Duader ST, Webber MM, Waalkes MP. Cadmium-induced malignant transfor-mation of human prostate epithelial cells. Cancer Res. 2001; 61:455–8.

    PubMed  CAS  Google Scholar 

  • Bonkhoff H, Remberger K. Widespread distribution of nuclear androgen receptors in the basal cell layer of the normal and hyperplastic human prostate. Virchows Arch A Pathol Anat. 1993:422:35–8.

    Article  CAS  Google Scholar 

  • Chodak GW, Kranc DM, Puy LA, Takeda H, Johnson K, Chang C. Nuclear localization of androgen receptor in heterogeneous samples of normal, hyperplastic and neo-plastic human prostate. JUrol. 1992:147:798–803.

    CAS  Google Scholar 

  • Cunha GR. Role of mesenchymal-epithelial interactions in normal and abnormal development of the mammary gland and prostate. Cancer. 1994:74:1030–44.

    Article  PubMed  CAS  Google Scholar 

  • Cunha GR, Donjacour AA, Cooke PS, et al. The endocrinology and developmental biology of the prostate. [Review]. Endocr Rev. 1987:8:338–62.

    Article  PubMed  CAS  Google Scholar 

  • Cunha GR, Hayward SW, Dahiya R, Foster BA. Smooth muscle-epithelial interactions in normal and neoplastic prostate development. Acta Anat. 1996:155:63–72.

    Article  PubMed  CAS  Google Scholar 

  • Dube JY, Chapdelaine P, Tremblay RR. Effect of testicular hormones on synthesisi of soluble proteins by dog prostate slices. Can J Biochem Cell Biol. 1983;61(7):756–63.

    Article  PubMed  CAS  Google Scholar 

  • English HF, Santen RJ, Isaacs JT. Response of glandular versus basal rat ventral prostatic epithelial cells to androgen with-drawal and replacement. Prostate. 1987:11:229–42.

    PubMed  CAS  Google Scholar 

  • Farnsworth WE. Activities of the androgen-responsive receptor of the prostatic plasma membrane. Invest Urol. 1977:15(1): 75–7.

    PubMed  CAS  Google Scholar 

  • Fisher RL, Nau H, Gandolfi AJ, Putnam CW, Brendel K. Valproic acid hepatotoxicity in human liver slices. Drug ChemToxicol. 1991a;14:375–94.

    CAS  Google Scholar 

  • Fisher RL, Hanziik RP, Gandolfi AJ, Brendel K. Toxicity of ortho-substituted bromobenzenes in rat liver slices: a com-parison to isolated hepatocytes and the whole animal. In VitroToxicol. 1991b;4:173–86.

    CAS  Google Scholar 

  • Fisher RL, Nau H, Gandolfi AJ, Brendel K. Toxicity of valproic acid in liver slices from Sprague-Dawley rats and domestic pigs. Toxicol InVitro. 1991c;5:201–5.

    Article  CAS  Google Scholar 

  • Geller J, Sionit LR, Connors K, Hoffinan RM. Measurement of androgen receptor sensitivity in the human prostate in vitro, three-dimensional histoculture. Prostate. 1992:21:269–78.

    PubMed  CAS  Google Scholar 

  • Geller J, Partido C, Sionit L, et al. Comparison of androgen-independent growth and androgen-dependent growth in BPH and cancer tissue from the same radical prostatec-tomies in sponge-gel matrix histoculture. Prostate. 1997:31: 250–4.

    Article  PubMed  CAS  Google Scholar 

  • Gown AM, Vogel AM. Monoclonal antibodies to human intermediate filament proteins: distribution of filament proteins in normal human tissues. Am J Pathol. 1984:114:309–21.

    PubMed  CAS  Google Scholar 

  • Greenberg NM, DeMayo F, Finegold MJ, et al. Prostate cancer in a transgenic mouse. Proc Nati Acad Sci USA. 1995:92: 3439–3.

    Article  CAS  Google Scholar 

  • Hampton JA, Selman SH. Mechanisms of cell killing in photodynamic therapy using a novel in vivo drug/in vitro light culture system. Photochem Photobiol. 1992;56(2):235–42.

    PubMed  CAS  Google Scholar 

  • Hayward SW, Rosen MA, Cunha GR. Stromal-epithelial interactions in the normal and neoplastic prostate. Br J Urol. 1997;79(Supplement 2):18–26.

    PubMed  Google Scholar 

  • Hairamatsu M, Kashimata M, Minami N, Sato A, Murayama M. Androgenic regulation of epidermal growth factor in the mouseventral prostate. Biochemint. 1998:17:311–7.

    Google Scholar 

  • Howat AJ, Mills PM, Lyons TJ, Stephenson TJ. Absence of S-100 proteins in prostatic glands. Histopathology. 1988;13: 468–70.

    PubMed  CAS  Google Scholar 

  • Isaacs JT, Coffey DS. Etiology and disease process of benign prostatic hyperplasia. Prostate Suppi. 1989:2:33–50.

    CAS  Google Scholar 

  • Kasper S, Sheppard PC, Yan Y, et al. Development, progression, and androgen-dependence of prostate tumors in probasin-large T antigen transgenic mice: a model for prostate cancer. Lab Invest. 1998:78:319–33.

    PubMed  CAS  Google Scholar 

  • Koenig H, Lu CY, Bakat R. Lysosomal enzyme secretion in rat ventral prostate. Acta Biol Med Germ. 1977:36 (11–12): 1653–9.

    PubMed  CAS  Google Scholar 

  • Leav I, McNeal JE, Kwan PW, Komminoth P, Merk FB. Androgen receptor expression in prostatic dysplasia (pro-static intraepithelial neoplasia) in the human prostate: an immunohistochemical and 171 situ hybridization study. Prostate. 1996:29:137–45.

    PubMed  CAS  Google Scholar 

  • Leong AS, Gilham P, Milos J. Cytokeratin and vimentin intermediate filament proteins in benign and neoplastic prostatic epithelium. Histopathology. 1988:13:435–42.

    PubMed  CAS  Google Scholar 

  • Maitland NJ, Macintosh CA, Hall J, Sharrard M, Quinn G, Lang S. In vitro models to study cellular differentiation and function in human prostate cancers. Radiat Res. 2001:155: 133–2.

    Article  PubMed  CAS  Google Scholar 

  • McCandless JR, Cress AE, Rabinovitz I, et al. A human xenograft model for testing early events of epithelial neo-plastic invasion. Int J Oncol. 1997:10:279–85.

    CAS  Google Scholar 

  • McNeal JE. Origin and development of carcinoma in the prostate. Cancer, 1969;23(l):24–34.

    Article  PubMed  CAS  Google Scholar 

  • McNeal JE. Normal histology of the prostate. Am J Surg Pathol. 1988:12:619–33.

    PubMed  CAS  Google Scholar 

  • Mettlin CJ, Murphy GP, Rosenthal DS, Menck HR. The national cancer data base report on prostate carcinoma after the peak in incidence rates in the U.S. Cancer. 1998; 83:1679–84.

    Article  PubMed  CAS  Google Scholar 

  • Montironi R, Bostwick DG, Bonkhoff H, et al. Origins of prostate cancer. Cancer. 1996;78(2):362–5.

    Article  PubMed  CAS  Google Scholar 

  • Olbina G, Miljkovic D, Hoffman RM, Geller J. New sensitive discovery histoculture model for growth-inhibition studies in prostate cancer and BPH. Prostate. 1998:37:126–9.

    Article  PubMed  CAS  Google Scholar 

  • Parrish AR, Shipp NG, Spall RD, et al. Organ culture of rat myocardial slices: an alternative 171 vitro tool in organ-specific toxicology. Toxicol Methods. 1992:2:101–11.

    CAS  Google Scholar 

  • Parrish AR, Gandolfi AJ, Brendel K. Precision-cut tissue slices: applications in pharmacology and toxicology. Life Sci. 1995:57:1887–901.

    Article  PubMed  CAS  Google Scholar 

  • Pretlow TG, Yang B, Pretlow TP. Organ culture of benign, aging and hyperplastic human prostate. Microsc Res Tech. 1995:30:271–81.

    Article  PubMed  CAS  Google Scholar 

  • Ruegg CE, Gandolfi AJ, Nagle RB, Brendel K. Differential patterns of injury to the proximal tubule of renal cortical slices following 171 vitro exposure to mercuric chloride, potassium dichromate, or hypoxic conditions. Toxicol Appi Pharmacol. 1987:90:261–73.

    Article  CAS  Google Scholar 

  • Ruizeveld de Winter JA, Janssen PJ, Sleddens HM, et al. Androgen receptor status in localized and locally progres-sive hormone refractory human prostate cancer. Am J Pathol. 1994:144:735–46.

    PubMed  CAS  Google Scholar 

  • Stonington OG, Hemmingsen H. Culture of cells as a mono-layer derived from the epithelium of the human prostate: a new cell growth technique. J Urol. 1971:106:393–400.

    PubMed  CAS  Google Scholar 

  • Varani J, Dame MK, Wojno K, Schuger L, Johnson KJ. Characteristics of nonmalignant and malignant human prostate in organ culture. Lab Invest. 1999;79(6):723–31.

    PubMed  CAS  Google Scholar 

  • Wolfgang GHI, Gandolfi AJ, Stevens JL, Brendel K. W-Acetyl-S(1,2-dichlorovinyl)-L-cysteine produces a similar toxicity to S-(l, 2-dichlorovinyD-L-cysteine in rabbit renal slices: differential transport and metabolism. Toxicol Appi Pharmacol. 1989:101:205–19.

    Article  CAS  Google Scholar 

  • Ye J, Wang S, Barger M, Castronova V, Shi X. Activation of androgen response element by cadmium: a potential me-chanism of a carcinogenic effect of cadmium in the prostate. J Environ Pathol Toxicol Oncol. 2000;19(3):275–80.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Parrish, A., Sallam, K., Nyman, D. et al. Culturing precision-cut human prostate slices as an in vitro model of prostate pathobiology. Cell Biol Toxicol 18, 205–219 (2002). https://doi.org/10.1023/A:1015567805460

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1015567805460

Navigation