Radiation and Environmental Biophysics

, Volume 57, Issue 2, pp 133–142 | Cite as

Evaluation of the effect of hyperthermia and electron radiation on prostate cancer stem cells

  • Zhila Rajaee
  • Samideh Khoei
  • Seied Rabi Mahdavi
  • Marzieh Ebrahimi
  • Sakine Shirvalilou
  • Alireza Mahdavian
Original Article

Abstract

The aim of this study was to investigate the effect of hyperthermia, 6 MeV electron radiation and combination of these treatments on cancer cell line DU145 in both monolayer culture and spheroids enriched for prostate cancer stem cells (CSCs). Flowcytometric analysis of the expression of molecular markers CD133+/CD44+ was carried out to determine the prostate CSCs in cell line DU145 grown as spheroids in serum-free medium. Following monolayer and spheroid culture, DU145 cells were treated with different doses of hyperthermia, electron beam and combination of them. The survival and self-renewing of the cells were evaluated by colony formation assay (CFA) and spheroid formation assay (SFA). Flowcytometry results indicated that the percentage of CD133+/CD44+ cells in spheroid culture was 13.9-fold higher than in the monolayer culture. The SFA showed significant difference between monolayer and spheroid culture for radiation treatment (6 Gy) and hyperthermia (60 and 90 min). The CFA showed significantly enhanced radiosensitivity in DU145 cells grown as monolayer as compared to spheroids, but no effect of hyperthermia. In contrast, for the combination of radiation and hyperthermia the results of CFA and SFA showed a reduced survival fraction in both cultures, with larger effects in monolayer than in spheroid culture. Thus, hyperthermia may be a promising approach in prostate cancer treatment that enhances the cytotoxic effect of electron radiation. Furthermore, determination and characterization of radioresistance and thermoresistance of CSCs in the prostate tumor is the key to develop more efficient therapeutic strategies.

Keywords

Prostate cancer Cancer stem cells DU145 cell line Electron radiation Hyperthermia 

Notes

Acknowledgements

This research was supported by Grant No. 20109 from the School of Medicine, Iran University of Medical Sciences (IUMS) and by Grant No. 92027547 from the Iran National Science Foundation (INSF).

Compliance with ethical standards

Conflict of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

References

  1. Ames SC et al (2008) Quality of life of men with biochemical recurrence of prostate cancer. J Psychosoc Oncol 26:17–34CrossRefGoogle Scholar
  2. Atanackovic D, Nierhaus A, Neumeier M, Hossfeld DK, Hegewisch-Becker S (2002) 41.8 C whole body hyperthermia as an adjunct to chemotherapy induces prolonged T cell activation in patients with various malignant diseases. Cancer Immunol Immunother 51:603–613CrossRefGoogle Scholar
  3. Autorino R, Di Lorenzo G, Damiano R, De Placido S, D’Armiento M (2003) Role of chemotherapy in hormone-refractory. Prostate Cancer Urologia Int 70:1–14CrossRefGoogle Scholar
  4. Barnhart BC, Simon MC (2007) Metastasis and stem cell pathways. Cancer Metastasis Rev 26:261–271CrossRefGoogle Scholar
  5. Baronzio G, Gramaglia A, Fiorentini G (2009) Current role and future perspectives of hyperthermia for prostate cancer treatment. in vivo 23:143–146Google Scholar
  6. Bensimon J et al (2016) Forced extinction of CD24 stem-like breast cancer marker alone promotes radiation resistance through the control of oxidative stress. Mol Carcinog 55:245–254CrossRefGoogle Scholar
  7. Buron C et al (2007) Brachytherapy versus prostatectomy in localized prostate cancer: results of a French multicenter prospective medico-economic study. Int J Radiat Oncol Biol Phys 67:812–822CrossRefGoogle Scholar
  8. Cao L et al (2011) Sphere-forming cell subpopulations with cancer stem cell properties in human hepatoma cell lines. BMC Gastroenterol 11:71.  https://doi.org/10.1186/1471-230X-11-71 ADSCrossRefGoogle Scholar
  9. Castellón EA et al (2012) Molecular signature of cancer stem cells isolated from prostate carcinoma and expression of stem markers in different Gleason grades metastasis. Biol Res 45:297–305CrossRefGoogle Scholar
  10. Clarke MF et al (2006) Cancer stem cells—perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res 66:9339–9344CrossRefGoogle Scholar
  11. Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ (2005) Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 65:10946–10951CrossRefGoogle Scholar
  12. Dey D et al. (2009) Phenotypic and functional characterization of human mammary stem/progenitor cells in long term culture. PloS One 4:e5329ADSCrossRefGoogle Scholar
  13. Diehn M et al (2009) Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature 458:780–783.  https://doi.org/10.1038/nature07733 ADSCrossRefGoogle Scholar
  14. Dobrucki J, Bleehen N (1985) Cell-cell contact affects cellular sensitivity to hyperthermia British. J Cancer 52:849CrossRefGoogle Scholar
  15. Dontu G, Abdallah WM, Foley JM, Jackson KW, Clarke MF, Kawamura MJ, Wicha MS (2003) In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev 17:1253–1270CrossRefGoogle Scholar
  16. Dubrovska A et al (2009) The role of PTEN/Akt/PI3K signaling in the maintenance and viability of prostate cancer stem-like cell populations. Proc Natl Acad Sci 106:268–273ADSCrossRefGoogle Scholar
  17. Fabian A, Barok M, Vereb G, Szöllősi J (2009) Die hard: are cancer stem cells the Bruce Willises of tumor biology? Cytometry Part A 75:67–74CrossRefGoogle Scholar
  18. Fan X, Liu S, Su F, Pan Q, Lin T (2012) Effective enrichment of prostate cancer stem cells from spheres in a suspension culture system. Urol Oncol 30:314–318CrossRefGoogle Scholar
  19. Fillmore CM, Kuperwasser C (2008) Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy. Breast Cancer Res 10:1CrossRefGoogle Scholar
  20. Franken NA, Barendsen GW (2014) Enhancement of radiation effectiveness by hyperthermia and incorporation of halogenated pyrimidines at low radiation doses as compared with high doses: implications for mechanisms International. J Radiat Biol 90:313–317CrossRefGoogle Scholar
  21. Gao F, Ye Y, Zhang Y, Yang J (2013) Water bath hyperthermia reduces stemness of colon cancer cells. Clin Biochem 46:1747–1750.  https://doi.org/10.1016/j.clinbiochem.2013.08.023 CrossRefGoogle Scholar
  22. Gomez-Casal R et al. (2013) Non-small cell lung cancer cells survived ionizing radiation treatment display cancer stem cell and epithelial-mesenchymal transition phenotypes. Mol Cancer 12:1CrossRefGoogle Scholar
  23. Haraguchi N, Inoue H, Tanaka F, Mimori K, Utsunomiya T, Sasaki A, Mori M (2006) Cancer stem cells in human gastrointestinal cancers. Human cell 19:24–29CrossRefGoogle Scholar
  24. Heidenreich A et al (2011) EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and treatment of clinically localised disease. Eur Urol 59:61–71CrossRefGoogle Scholar
  25. Hurt EM, Kawasaki BT, Klarmann GJ, Thomas SB, Farrar WL (2008) CD44+ CD24—prostate cells are early cancer progenitor/stem cells that provide a model for patients with poor prognosis. Br J Cancer 98:756–765CrossRefGoogle Scholar
  26. Johannsen M et al (2007) Thermotherapy of prostate cancer using magnetic nanoparticles: feasibility, imaging, and three-dimensional temperature distribution. Eur Urol 52:1653–1662CrossRefGoogle Scholar
  27. Khoei S, Goliaei B, Neshasteh-Riz A, Deizadji A (2004) The role of heat shock protein 70 in the thermoresistance of prostate cancer cell line spheroids. FEBS Lett 561:144–148.  https://doi.org/10.1016/S0014-5793(04)00158-9 CrossRefGoogle Scholar
  28. Khoei S, Azarian M, Khoee S (2012) Effect of hyperthermia and triblock copolymeric nanoparticles as quercetin carrier on DU145 prostate cancer cells. Current Nanosci 8:690–696ADSCrossRefGoogle Scholar
  29. Kyjacova L et al (2015) Radiotherapy-induced plasticity of prostate cancer mobilizes stem-like non-adherent, Erk signaling-dependent cells. Cell Death Differ 22:898–911CrossRefGoogle Scholar
  30. Li H, Tang DG (2011) Prostate cancer stem cells and their potential roles in metastasis. J Surg Oncol 103:558–562CrossRefGoogle Scholar
  31. Mottet N et al (2011) EAU guidelines on prostate cancer. Part II: Treatment of advanced, relapsing, and castration-resistant prostate cancer. Actas Urológicas Españolas (English Edition) 35:565–579CrossRefGoogle Scholar
  32. Ngugi PM, Magoha GA (2007) The management of early prostate cancer: a review East. Afr Med J 84:S24-30Google Scholar
  33. Niciforovic A, Djordjevic J, Adzic M, Vucic V, Mitrasinovic PM, Radojcic MB (2008) Experimental and systems biology studies of the molecular basis for the radioresistance of prostate carcinoma cells. Ann Biomed Eng 36:831–838CrossRefGoogle Scholar
  34. Overgaard J (1989) The current and potential role of hyperthermia in radiotherapy International. J Radiat Oncol Biol Phys 16:535–549CrossRefGoogle Scholar
  35. Pelicci PG, Dalton P, Orecchia R (2011) Heating cancer stem cells to reduce tumor relapse. Breast Cancer Res 13:305CrossRefGoogle Scholar
  36. Puck TT, Marcus PI (1956) Action of X-rays on mammalian cells. J Exp Med 103:653–666CrossRefGoogle Scholar
  37. Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer and cancer stem cells. Nature 414:105–111ADSCrossRefGoogle Scholar
  38. Reynolds BA, Rietze RL (2005) Neural stem cells and neurospheres—re-evaluating the relationship. Nat Methods 2:333–336CrossRefGoogle Scholar
  39. Ryu S, Brown SL, Kim S-H, Khil MS, Kim JH (1996) Preferential radiosensitization of human prostatic carcinoma cells by mild hyperthermia. Int J Radiat Oncol Biol Phys 34:133–138CrossRefGoogle Scholar
  40. Siegel RL, Miller KD, Jemal A (2015) Cancer statistics, 2015. CA Cancer J Clin 65:5–29.  https://doi.org/10.3322/caac.21254 CrossRefGoogle Scholar
  41. Skitzki JJ, Repasky EA, Evans SS (2009) Hyperthermia as an immunotherapy strategy for cancer. Curr Opin Invest Drugs (London: 2000) 10:550Google Scholar
  42. Skvortsova I et al (2008) Intracellular signaling pathways regulating radioresistance of human prostate carcinoma cells. Proteomics 8:4521–4533CrossRefGoogle Scholar
  43. Sun L, Cabarcas SM, Farrar WL (2012) Radioresistance and cancer stem cells: survival of the fittest. J Carcinog Mutagen S1:004.  https://doi.org/10.4172/2157-2518.S1-004 Google Scholar
  44. Tirino V et al (2013) Cancer stem cells in solid tumors: an overview and new approaches for their isolation and characterization. FASEB J 27:13–24CrossRefGoogle Scholar
  45. Tu S-M, Lin S-H (2012) Prostate cancer stem cells. Clin Genitourin Cancer 10:69–76CrossRefGoogle Scholar
  46. Van Vulpen M et al (2003) A prospective quality of life study in patients with locally advanced prostate cancer, treated with radiotherapy with or without regional or interstitial hyperthermia. Int J Hyperth 19:402–413CrossRefGoogle Scholar
  47. van Tol-Geerdink JJ et al (2006) Systematic review of the effect of radiation dose on tumor control and morbidity in the treatment of prostate cancer by 3D-CRT International. J Radiat Oncol Biol Phys 64:534–543CrossRefGoogle Scholar
  48. Wang L et al (2013) Enrichment of prostate cancer stem-like cells from human prostate cancer cell lines by culture in serum-free medium and chemoradiotherapy. Int J Biol Sci 9:472–479CrossRefGoogle Scholar
  49. Woodward WA, Bristow RG (2009) Radiosensitivity of cancer-initiating cells and normal stem cells (or what the Heisenberg uncertainly principle has to do with biology). In: Seminars in radiation oncology. vol 2. Elsevier, Amsterdam, pp 87–95Google Scholar
  50. Yu C, Yao Z, Jiang Y, Keller ET (2012) Prostate cancer stem cell biology. Minerva urologica e nefrologica 64:19Google Scholar
  51. Zhang L et al (2012) Tumorspheres derived from prostate cancer cells possess chemoresistant and cancer stem cell properties. J Cancer Res Clin Oncol 138:675–686CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Medical Physics, School of MedicineIran University of Medical SciencesTehranIran
  2. 2.Department of Stem Cells and Developmental Biology, Cell Science Research CentreRoyan Institute for Stem Cell Biology and Technology, ACECRTehranIran
  3. 3.Polymer Science DepartmentIran Polymer and Petrochemical InstituteTehranIran

Personalised recommendations