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A common effect of angiotensin II and relaxin 2 on the PNT1A normal prostate epithelial cell line

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Abstract

The prostate gland is a part of the male reproductive tract which produces both angiotensin II (Ang II) and relaxin 2 (RLN2). The present study analyzes the effect of both these peptide hormones at concentration 10−8M on viability, proliferation, adhesion, migration, and invasion of normal prostate epithelial cells (PNT1A). Improved survival in two- and three-dimensional cell cultures was noted as well as visual changes in colony size and structure in Geltrex™. Stimulatory influence on cell viability of each peptide applied single was lower than in combination. Enhanced survival of PNT1A cells appears to be associated with increased BCL2/BAX messenger RNA (mRNA) expression ratio. Modulation of cell spreading and cell-extracellular matrix adhesion dynamics were also altered as an influence of tested hormone application. However, long-term Ang II and RLN2 effects may lead to an increase of normal prostate cell migration and invasion abilities. Moreover, gelatin zymography revealed that both gelatinases A and B were augmented by Ang II treatment, whereas RLN2 significantly stimulated only MMP-9 secretion. These results support the hypothesis that deregulation of locally secreted peptide hormones such as Ang II and RLN2 may take part in the development of certain cancers, including prostate cancer. Moreover, the observed ability of relaxin 2 to act as a regulator of mRNA expression levels not only LGR7 but also classic angiotensin receptors suggested that renin-angiotensin system and relaxin family peptide system are functionally linked.

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References

  1. Avancès C, Georget V, Térouanne B, Orio F, Cussenot O, Mottet N, Costa P, Sultan C (2001) Human prostatic cell line PNT1A a useful tool for studying androgen receptor transcriptional activity and its differential subnuclear localization in the presence of androgens and antiandrogens. Mol Cell Endocrinol 184:13–24

    Article  PubMed  Google Scholar 

  2. Chow BS, Kocan M, Bosnyak S, Sarwar M, Wigg B, Jones ES, Widdop RE, Summers RJ, Bathgate RA, Hewitson TD, Samuel CS (2014) Relaxin requires the angiotensin II type 2 receptor to abrogate renal interstitial fibrosis. Kidney Int 86:75–85

    Article  CAS  PubMed  Google Scholar 

  3. Dahl KN, Ribeiro AJ, Lammerding J (2008) Nuclear shape mechanics and mechanotransduction. Circ Res 102:1307–1318

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Degeorges A, Hoffschir F, Cussenot O, Gauville C, Le Duc A, Dutrillaux B, Calvo F (1995) Recurrent cytogenetic alterations of prostate carcinoma and amplification of c-myc or epidermal growth factor receptor in subclones of immortalized PNT1 human prostate epithelial cell line. Int J Cancer 62:724–731

    Article  CAS  PubMed  Google Scholar 

  5. Domińska K (2009) The importance of the local rennin-angiotensin system in the pathology of prostate. Folia Medica Lodziensia 36:73–86

    Google Scholar 

  6. Domińska K (2013) Relaxin 2—a pregnancy hormone involved in the process of carcinogenesis. Ginekol Pol 84:126–130

    PubMed  Google Scholar 

  7. Domińska K, Lachowicz-Ochedalska A (2008) The involvement of the renin-angiotensin system (RAS) in cancerogenesis. Postepy Biochem 54:294–300

    PubMed  Google Scholar 

  8. Domińska K, Piastowska AW, Rebas E, Lachowicz-Ochedalska A (2009) The influence of peptides from the angiotensin family on tyrosine kinase activity and cell viability in a human hormone-dependent prostate cancer line. Endokrynol Pol 60:363–9

    PubMed  Google Scholar 

  9. Domińska K, Piastowska-Ciesielska AW, Lachowicz-Ochędalska A, Ochędalski T (2012) Similarities and differences between effects of angiotensin III and angiotensin II on human prostate cancer cell migration and proliferation. Peptides 37:200–206

    Article  PubMed  Google Scholar 

  10. Dominska K, Piastowska-Ciesielska AW, Pluciennik E, Lachowicz-Ochedalska A, Ochedalski T (2013) A comparison of the effects of Angiotensin IV on androgen-dependent and androgen-independent prostate cancer cell lines. J Renin Angiotensin Aldosterone Syst 14:74–81

    Article  CAS  PubMed  Google Scholar 

  11. Dschietzig T, Bartsch C, Baumann G, Stangl K (2006) Relaxin—a pleiotropichormone and its emerging role for experimental and clinical therapeutics. Pharmacol Ther 112:38–56

    Article  CAS  PubMed  Google Scholar 

  12. Feng S, Agoulnik IU, Bogatcheva NV, Kamat AA, Kwabi-Addo B, Li R, Ayala G, Ittmann MM, Agoulnik AI (2007) Relaxin promotes prostate cancer progression. Clin CancerRes 13:1695–1702

    Article  CAS  Google Scholar 

  13. Ferlin A, Menegazzo M, Gianesello L, Selice R, Foresta C (2012) Effect of relaxin on human sperm functions. J Androl 33:474–482

    Article  CAS  PubMed  Google Scholar 

  14. Ferreira VM, Gomes TS, Reis LA, Ferreira AT, Razvickas CV, Schor N, Boim MA (2009) Receptor-induced dilatation in the systemic and intrarenal adaptation to pregnancy in rats. PLoS One 4:e4845

    Article  PubMed  PubMed Central  Google Scholar 

  15. Frederiks WM, Mook OR (2004) Metabolic mapping of proteinase activity with emphasis on in situ zymography of gelatinases: review and protocols. J Histochem Cytochem 52:711–722

    Article  CAS  PubMed  Google Scholar 

  16. Friedl P, Wolf K (2003) Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer 3:362–374

    Article  CAS  PubMed  Google Scholar 

  17. Geddes BJ, Summerlee AJ (1995) The emerging concept of relaxin as a centrally acting peptide hormone with hemodynamic actions. J Neuroendocrinol 7:411–417

    Article  CAS  PubMed  Google Scholar 

  18. George AJ, Thomas WG, Hannan RD (2010) The renin-angiotensin system and cancer: old dog new tricks. Nat Rev Cancer 10:745–759

    Article  CAS  PubMed  Google Scholar 

  19. Guilluy C, Osborne LD, Van Landeghem L, Sharek L, Superfine R, Garcia-Mata R, Burridge K (2014) Isolated nuclei adapt to force and reveal a mechanotransduction pathway in the nucleus. Nat Cell Biol 16:376–381

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hadler-Olsen E, Winberg JO, Uhlin-Hansen L (2013) Matrix metalloproteinases in cancer: their value as diagnostic and prognostic markers and therapeutic targets. Tumor Biol 34:2041–2051

    Article  CAS  Google Scholar 

  21. Härmä V, Virtanen J, Mäkelä R, Happonen A, Mpindi JP, Knuuttila M, Kohonen P, Lötjönen J, Kallioniemi O, Nees M (2010) A comprehensive panel of three-dimensional models for studies of prostate cancer growth invasion and drug responses. PLoS One 5:e10431

    Article  PubMed  PubMed Central  Google Scholar 

  22. Haulica I, Bild W, Serban DN (2005) Angiotensin peptides and their pleiotropicactions. J Renin Angiotensin Aldosterone Syst 6:121–131

    Article  CAS  PubMed  Google Scholar 

  23. Hongisto V, Jernström S, Fey V, Mpindi JP, Sahlberg KK, Kallioniemi O, Perälä M (2013) High-throughput 3D screening reveals differences in drug sensitivities between culture models of JIMT1 breast cancer cells. PLoS One 8:e77232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ivell R, Kotula-Balak M, Glynn D, Heng K, Anand-Ivell R (2011) Relaxin family peptides in the male reproductive system—a critical appraisal. Mol Hum Reprod 17:71–84

    Article  CAS  PubMed  Google Scholar 

  25. Leung PS, Sernia C (2003) The renin-angiotensin system and male reproduction: new functions for old hormones. J MolEndocrinol 30:263–270

    Article  CAS  Google Scholar 

  26. Lin Y, Fukuchi J, Hiipakka RA, Kokontis JM, Xiang J (2007) Up-regulation of Bcl-2 is required for the progression of prostate cancer cells from an androgen-dependent to an androgen-independent growth stage. Cell Res 17:531–536

    Article  CAS  PubMed  Google Scholar 

  27. Mazaris E, Tsiotras A (2013) Molecular pathways in prostate cancer. Nephrourol Mon 5:792–800

    Article  PubMed  PubMed Central  Google Scholar 

  28. Mitchell S, Abel P, Ware M, Stamp G, Lalani E (2000) Phenotypic and genotypic characterization of commonly used human prostatic cell lines. BJU Int 85:932–944

    Article  CAS  PubMed  Google Scholar 

  29. O’Mahony OA, Barker S, Puddefoot JR, Vinson GP (2005) Synthesis and secretion of angiotensin II by the prostate gland in vitro. Endocrinology 146:392–398

    Article  PubMed  Google Scholar 

  30. Piastowska-Ciesielska AW, Dominska K, Nowakowska M, Gajewska M, Gajos-Michniewicz A, Ochedalski T (2013) Angiotensin modulates human mammary epithelial cell motility. J Renin Angiotensin Aldosterone Syst 15:419–429

    Article  PubMed  Google Scholar 

  31. Pluciennik E, Krol M, Nowakowska M, Kusinska R, Potemski P, Kordek R, Bednarek AK (2010) Breast cancer relapse prediction based on multi-gene RT-PCR algorithm. Med Sci Monit 16:CR132–136

    PubMed  Google Scholar 

  32. Schrecengost R, Knudsen KE (2013) Molecular pathogenesis and progression of prostate cancer. SeminOncol 40:244–258

    CAS  Google Scholar 

  33. Schwab TS, Stewart T, Lehr J, Pienta KJ, Rhim JS, Macoska JA (2000) Phenotypic characterization of immortalized normal and primary tumor derived human prostate epithelial cell cultures. Prostate 44:164–171

    Article  CAS  PubMed  Google Scholar 

  34. Silvertown JD, Summerlee AJ, Klonisch T (2003) Relaxin-like peptides in cancer. Int J Cancer 107:513–519

    Article  CAS  PubMed  Google Scholar 

  35. Teichman SL, Unemori E, Dschietzig T, Conrad K, Voors AA, Teerlink JR, Felker GM, Metra M, Cotter G (2009) Relaxin a pleiotropic vasodilator for the treatment of heart failure. Heart Fail Rev 4:321–329

    Article  Google Scholar 

  36. Tolonen TT, Tommola S, Jokinen S, Parviainen T, Martikainen PM (2007) Bax and Bcl-2 are focally overexpressed in the normal epithelium of cancerous prostates. Scand J UrolNephrol 41:85–90

    Article  Google Scholar 

  37. Tyson DR, Inokuchi J, Tsunoda T, Lau A, Ornstein DK (2007) Culture requirements of prostatic epithelial cell lines for acinar morphogenesis and lumen formation in vitro: role of extracellular calcium. Prostate 67:1601–1613

    Article  CAS  PubMed  Google Scholar 

  38. Uemura H, Ishiguro H, Nagashima Y, Sasaki T, Nakaigawa N, Hasumi H, Kato S, Kubota Y (2005) Antiproliferative activity of angiotensin II receptor blocker through cross-talk between stromal and epithelial prostate cancer cells. Mol Cancer Ther 4:1699–1709

    Article  CAS  PubMed  Google Scholar 

  39. Wu X, Gong S, Roy-Burman P, Lee P, Culig Z (2013) Current mouse and cell models in prostate cancer research. Endocr Relat Cancer 20:R155–170

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was financially supported by the National Science Center, research grant: NN403 2081 39.

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Authors and Affiliations

  1. Department of Comparative Endocrinology, Medical University of Lodz, ul. Zeligowskiego 7/9, 90-752, Lodz, Poland

    Kamila Domińska, Tomasz Ochędalski, Karolina Kowalska, Zuzanna E. Matysiak-Burzyńska & Agnieszka W. Piastowska-Ciesielska

  2. Department of Molecular Cancerogenesis, Medical University of Lodz, ul. Zeligowskiego 7/9, 90-752, Lodz, Poland

    Elżbieta Płuciennik

Authors
  1. Kamila Domińska
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  2. Tomasz Ochędalski
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  3. Karolina Kowalska
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  4. Zuzanna E. Matysiak-Burzyńska
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  5. Elżbieta Płuciennik
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  6. Agnieszka W. Piastowska-Ciesielska
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Correspondence to Kamila Domińska.

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Domińska, K., Ochędalski, T., Kowalska, K. et al. A common effect of angiotensin II and relaxin 2 on the PNT1A normal prostate epithelial cell line. J Physiol Biochem 72, 381–392 (2016). https://doi.org/10.1007/s13105-016-0489-1

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  • DOI: https://doi.org/10.1007/s13105-016-0489-1

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