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Peyronie's disease cell culture models: phenotypic, genotypic and functional analyses

International Journal of Impotence Research volume 14, pages 397–405 (2002)Cite this article

Abstract

Peyronie's disease is a fibromatosis of the tunica albuginea. While trauma is believed to be the inciting event, the exact pathophysiology of this condition is unknown. In vitro analysis of cell biology can shed light on the pathogenesis of medical conditions and has been used for many decades as a research tool. We have established a cell culture model, which we have used to study the pathobiology of cells derived from Peyronie's disease plaque tissue. In 10 separate cell cultures derived from different individuals, these cells have demonstrated consistent phenotypic, genotypic and functional alterations. In neither of the control cell cultures, neonatal foreskin fibroblasts and normal tunica-derived fibroblasts have any of the above aberrations been demonstrated. The cells studied have been shown to be fibroblasts in nature with a sub-population of myofibroblasts present in culture. The Peyronie's disease plaque tissue-derived fibroblasts have demonstrated (i) consistent morphologic transformation (ii) increased S-phase on flow cytometry (iii) decreased dependence on culture medium (iv) cytogenic instability (v) excess production of fibrogenic cytokines and (vi) stabilization and dysfunctionalization of p53. Further refinement of this model and future analyses may permit an increased understanding of the pathogenesis of this condition and allow the development of therapeutic strategies.

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References

  1. Schwarzer U et al. Prevalence of Peyronie's disease: results of an 8000 man survey J Urol 2000 163: 167

    Google Scholar 

  2. Jordan G . Peyronie's disease In: Walsh PC, ed Campbell's urology WB Saunders: Philadelphia 1992 pp 2204–2222

    Google Scholar 

  3. Gelbard MK, Dorey F, James K . The natural history of Peyronie's disease J Urol 1990 144: 1376–1382

    Article  CAS  PubMed  Google Scholar 

  4. Devine CJJ, Somers RD, Lagoda LE . Peyronie's disease: pathophysiology Prog Clin Biol Res 1991 370: 355–358

    PubMed  Google Scholar 

  5. Devine CJJ, Jordan GH, Somers RD . Peyronie's disease: cause and surgical treatment AUA Today 1989 2: 1–7

    Google Scholar 

  6. Chilton CP, Castle WM, Westwood CA, Pryor JP . Factors associated in the etiology of Peyronie's disease Br J Urol 1982 54: 748–751

    Article  CAS  PubMed  Google Scholar 

  7. Weidner W, Schroeder-Printzen I, Weiske W, Vosshenrich R . Sexual dysfunction in Peyronie's disease: an analysis of 222 patients without previous local plaque therapy J Urol 1997 157: 325–328

    Article  CAS  PubMed  Google Scholar 

  8. Alman RA et al. Aggressive fibromatosis J Pediatr Orthop 1992 12: 1–10

    Article  CAS  PubMed  Google Scholar 

  9. Vande Berg JS, Devine CJ Jr, Horton CE . Mechanisms of calcification in Peyronie's disease J Urol 1982 127: 52–54

    Article  CAS  PubMed  Google Scholar 

  10. Liang SB et al. Tetrasomy 12 in ovarian tumors of the coma-fibroma group: a fluorescence in situ hybridization analysis using paraffin sections Pathol Int 2001 51: 37–42

    Article  CAS  PubMed  Google Scholar 

  11. Ralph DJ, Mirakian R, Pryor JP, Bottazzo GF . The immunological features of Peyronie's disease J Urol 1996 155: 159–162

    Article  CAS  PubMed  Google Scholar 

  12. Devine CJJ, Somers KD, Jordan GH, Scholssberg SM . Proposal: trauma as the cause of Peyronie's lesion J Urol 1997 157: 285–290

    Article  PubMed  Google Scholar 

  13. Leffell MS et al. Non-association of Peyronie's disease with HLA B7 cross-reactive antigens J Urol 1982 127: 1223–1224

    Article  CAS  PubMed  Google Scholar 

  14. Nachsteim DA, Rearden A . Peyronie's disease is associated with an HLA class II antigen HLA-DQ5, implying an autoimmune etiology J Urol 1996 156: 1330

    Article  Google Scholar 

  15. El-Sakka AI et al. An animal model of Peyronie's-like condition associated with an increase of TGF beta mRNA and protein expression J Urol 1997 158: 2284–2290

    Article  CAS  PubMed  Google Scholar 

  16. Mulhall JP, Thom J, Lubrano T, Shankey TV . Basic fibroblast growth factor expression in Peyronie's disease J Urol 2001 165: 419–423

    Article  CAS  PubMed  Google Scholar 

  17. Yamanaka M et al. Genetic instability in Peyronie's disease J Urol 2001 165: 201

    Google Scholar 

  18. Pierpaoli S et al. Chromosomal instability in Peyronie's disease plaques: preliminary data J Urol 1998 159: 362A

    Article  Google Scholar 

  19. Mulhall JP, Thom J, Lubrano T, Shankey TV . Cytogenetic evidence in support of Peyronie's disease being a tunical field defect process J Urol 2000 163: 747A

    Google Scholar 

  20. Somers KD et al. Cell culture of Peyronie's disease plaque and normal penile tissue J Urol 1982 127: 585–588

    Article  CAS  PubMed  Google Scholar 

  21. Smith BH . Peyronie's disease Am J Clin Path 1966 45: 670–674

    Article  CAS  PubMed  Google Scholar 

  22. Brock G et al. The anatomy of the tunica albuginea in the normal penis and Peyronie's disease J Urol 1997 151: 276–281

    Article  Google Scholar 

  23. Devine CJJ, Angemeir RW . Anatomy of the penis and male perineum AUA Update 1993 12: 1–6

    Google Scholar 

  24. El-Sakka AI et al. Histological and ultrastructural alterations in an animal model of Peyronie's disease Br J Urol 1998 81: 445–452

    Article  CAS  PubMed  Google Scholar 

  25. Vernet D et al. Differentiation phenotype of myofibroblasts from penile tuncia albuginea J Urol 2001 165: 200

    Google Scholar 

  26. Bridge JA et al. Clonal chromosomal abnormalities in desmoid tumors. Implications for histopathogenesis Cancer 1992 69: 430–436

    Article  CAS  PubMed  Google Scholar 

  27. Rudolph R, Vande Berg J . The myofibroblast in Dupuytren's contracture Hand Clin N Am 1991 7: 683–692

    CAS  Google Scholar 

  28. Bowser-Riley S, Bain AD, Noble J, Lamb DW . Chromosome abnormalities in Dupuytren's disease Lancet 1975 2: 1282–1283

    Article  CAS  PubMed  Google Scholar 

  29. Mosmann T . Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays J Immun Methods 1983 65: 55–58

    Article  CAS  Google Scholar 

  30. El-Sakka A et al. The effects of colchicine on a Peyronie's-like condition in an animal model J Urol 1999 161: 1980–1983

    Article  CAS  PubMed  Google Scholar 

  31. Levine LA . Treatment of Peyronie's disease with intralesional verapamil injection J Urol 1997 158: 1395–1399

    Article  CAS  PubMed  Google Scholar 

  32. Wegner HE, Andersen R, Knipsel HH, Miller K . Treatment of Peyronie's disease with local interferon-alpha 2b Eur Urol 1995 28: 236–240

    Article  CAS  PubMed  Google Scholar 

  33. Anderson MS, Shankey TV, Lubrano T, Mulhall JP . Inhibition of Peyronie's plaque fibroblast proliferation by biologic agents Int J Impot Res 2000 12: (Suppl 3) S25–31

    Article  PubMed  Google Scholar 

  34. Cross SM et al. A p53-dependent mouse spindle checkpoint Science 1995 267: 1353–1356

    Article  CAS  PubMed  Google Scholar 

  35. Ioakim-Liossi A et al. p53 Protein expression and oestrogen and progesterone receptor status in invasive ductal breast carcinomas Cytopathology 2001 12: 197–202

    Article  CAS  PubMed  Google Scholar 

  36. Leite KR et al. Abnormal expression of mdm2 in prostate carcinoma Mod Pathol 2001 14: 428–436

    Article  CAS  PubMed  Google Scholar 

  37. Levine AJ . p53, the cellular gatekeeper for growth and division Cell 1997 88: 323–331

    Article  CAS  PubMed  Google Scholar 

  38. Cordon-Cardo C et al. p53 Mutations in human bladder cancer genotypic versus phenotypic patterns Int J Biochem Cell Biol 1994 56: 347–350

    CAS  Google Scholar 

  39. Campomenosi P et al. p53 Mutants can often transactivate promoters containing a p21 but not Bax or PIG3 responsive elements Oncogene 2001 20: 3573–3579

    Article  CAS  PubMed  Google Scholar 

  40. Hoos A et al. Characterization of molecular abnormalities in human fibroblastic neoplasms: a model for genotype-phenotype association in soft tissue tumors Cancer Res 2001 61: 3171–3175

    CAS  PubMed  Google Scholar 

  41. Halberg RB et al. Tumorigenesis in the multiple intestinal neoplasia mouse: redundancy of negative regulators and specificity of modifiers Proc Natl Acad Sci USA 2000 97: 3461–3466

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Moffatt EJ, Kerns BJ, Madden JM, Layfield LJ . Prognostic factors for fibromatoses: a correlation of proliferation index, estrogen receptor, p53, retinoblastoma, and src gene products and clinical features with outcome J Surg Oncol 1997 65: 117–122

    Article  CAS  PubMed  Google Scholar 

  43. Muller E et al. Molecular genetic and immunohistochemical analysis of the tumor suppressor genes Rb and p53 in palmar and aggressive fibromatosis Diagn Mol Pathol 1996 5: 194–200

    Article  CAS  PubMed  Google Scholar 

  44. Mulhall JP, Branch J, Lubrano T, Shankey TV . Perturbations of cell cycle regulators in Peyronie's disease Int J Impot Res 2001 13: (Suppl 5) S21–S28

    Article  PubMed  Google Scholar 

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Acknowledgements

Experiments outlined in this paper that were conducted at the Andrology Research Laboratory were funded by a Veterans Administration Career Development Award to Dr Mulhall.

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Authors and Affiliations

  1. Andrology Research Laboratory, Hines VA, Hines, Illinois, USA

    J P Mulhall, M S Anderson, T Lubrano & T V Shankey

  2. Department of Urology, Weill Medical College of Cornell University, The New York Hospital, 525 East 68th St, New York, 10021, NY

    J P Mulhall, M S Anderson & T V Shankey

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  4. T V Shankey
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Mulhall, J., Anderson, M., Lubrano, T. et al. Peyronie's disease cell culture models: phenotypic, genotypic and functional analyses. Int J Impot Res 14, 397–405 (2002). https://doi.org/10.1038/sj.ijir.3900874

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