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Prostate Cancer Spheroids: A Three-Dimensional Model for Studying Tumor Heterogeneity

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Cancer Cell Signaling

Abstract

Prostate cancer is one of the main causes of cancer and the sixth cause of death among men worldwide. One of the major challenges in prostate cancer research is cell heterogeneity defined as the different genomic and phenotypic characteristics in each individual cell making more difficult to assess the proper prostate cancer diagnosis and therapy. Tumor 3D spatial arrangement allow a strong interaction between the different cellular lineages and components which modulate cell proliferation, differentiation, and morphology. Prostate cancer spheroids are a cellular model which is capable to mimic the mechanical tensions of tumor tissue, providing a more representative pathophysiological model than the use of conventional 2D culture. Here, we describe a protocol to develop a 3D model of spheroids using prostate cancer cell lines (LNCaP, PC3, VCaP) which can be used to improve research considering tumoral heterogeneity role in cancer development, prognosis, and therapy.

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References

  1. GLOBOCAN (2018) Prostate cancer incidence, mortality and prevalence worldwide in 2018, GLOBOCAN Project. http://globocan.iarc.fr/

  2. Patrawala L, Calhoun-Davis T, Schneider-Broussard R, Tang DG (2007) Hierarchical organization of prostate cancer cells in xenograft tumors: the CD44+α2β1+ cell population is enriched in tumor-initiating cells. Cancer Res 67(14):6796–6805. https://doi.org/10.1158/0008-5472.CAN-07-0490

    Article  CAS  PubMed  Google Scholar 

  3. Tolkach Y, Kristiansen G (2018) The heterogeneity of prostate cancer: a practical approach. Pathobiology 85(1–2):108–116. https://doi.org/10.1159/000477852

    Article  CAS  PubMed  Google Scholar 

  4. Chambers KF, Mosaad EMO, Russell PJ, Clements JA, Doran MR (2014) 3D cultures of prostate cancer cells cultured in a novel high-throughput culture platform are more resistant to chemotherapeutics compared to cells cultured in monolayer. PLoS One 9(11):e111029. https://doi.org/10.1371/journal.pone.0111029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Donaldson JT, Tucker A, Keane TE, Walther PJ, Webb KS (1990) Characterization of a new model of human prostatic cancer: the multicellular tumor spheroid. Int J Cancer 46(2):238–244

    Article  CAS  PubMed  Google Scholar 

  6. Lee SH, Hu W, Matulay JT, Silva MV, Owczarek TB et al (2018) Tumor evolution and drug response in patient-derived organoid models of bladder cancer. Cell 173(2):515–528.e17. https://doi.org/10.1016/j.cell.2018.03.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Weiswald LB, Bellet D, Dangles-Marie V (2015) Spherical cancer models in tumor biology. Neoplasia 17(1):1–15

    Article  PubMed  PubMed Central  Google Scholar 

  8. Costa EC, Gaspar VM, Coutinho P, Correia IJ (2014) Optimization of liquid overlay technique to formulate heterogenic 3D co-cultures models. Biotechnol Bioeng 111(8):1672–1685

    Article  CAS  PubMed  Google Scholar 

  9. Costa EC, Moreira AF, de Melo-Diogo D, Gaspar VM, Carvalho MP, Correia IJ (2016) 3D tumor spheroids: an overview on the tools and techniques used for their analysis. Biotechnol Adv 34(8):1427–1441

    Article  PubMed  Google Scholar 

  10. Zanoni M, Piccinini F, Arienti C, Zamagni A, Santi S, Polico R et al (2016) 3D tumor spheroid models for in vitro therapeutic screening: a systematic approach to enhance the biological relevance of data obtained. Sci Rep 6:1–11

    Article  Google Scholar 

  11. Takagi A, Watanabe M, Ishii Y, Morita J, Hirokawa Y, Matsuzaki T, Shiraishi T (2007) Three-dimensional cellular spheroid formation provides human prostate tumor cells with tissue-like features. Anticancer Res 27(1A):45–54

    CAS  PubMed  Google Scholar 

  12. Breslin S, O’Driscoll L (2013) Three-dimensional cell culture: the missing link in drug discovery. Drug Discov Today 18(5–6):240–249

    Article  CAS  PubMed  Google Scholar 

  13. Lv D, Hu Z, Lu L, Lu H, Xu X (2017) Three-dimensional cell culture: a powerful tool in tumor research and drug discovery. Oncol Lett 14(6):6999–7010

    PubMed  PubMed Central  Google Scholar 

  14. Ballangrud AM, Yang WH, Dnistrian A, Lampen NM, Sgouros G (1999) Growth and characterization of LNCaP prostate cancer cell spheroids. Clin Cancer Res 5(10 Suppl):3171s–3176s

    CAS  PubMed  Google Scholar 

  15. 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(3):314–318

    Article  CAS  PubMed  Google Scholar 

  16. Mittler F, Obeïd P, Rulina AV, Haguet V, Gidrol X, Balakirev MY (2017) High-content monitoring of drug effects in a 3D spheroid model. Front Oncol 7:293. https://doi.org/10.3389/fonc.2017.00293

    Article  PubMed  PubMed Central  Google Scholar 

  17. Oktem G, Bilir A, Uslu R, Inan SV, Demiray SB, Atmaca H et al (2014) Expression profiling of stem cell signaling alters with spheroid formation in CD133(high)/CD44(high) prostate cancer stem cells. Oncol Lett 7(6):2103–2109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gao D, Vela I, Sboner A, Iaquinta PJ, Karthaus WR, Gopalan A et al (2014) Organoid cultures derived from patients with advanced prostate cancer. Cell 159(1):176–187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lukacs RU, Goldstein AS, Lawson DA, Cheng D, Witte ON (2010) Isolation, cultivation and characterization of adult murine prostate stem cells. Nat Protoc 5(4):702–713

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wang S, Huang S, Zhao X, Zhang Q, Wu M, Sun F et al (2014) Enrichment of prostate cancer stem cells from primary prostate cancer cultures of biopsy samples. Int J Clin Exp Pathol 7(1):184–193

    PubMed  Google Scholar 

  21. Vazquez-Santillan K, Melendez-Zajgla J, Jimenez-Hernandez LE, Gaytan-Cervantes J, Munõz-Galindo L, Pinã-Sanchez P et al (2016) NF-kappa B-inducing kinase regulates stem cell phenotype in breast cancer. Sci Rep 6:1–17. https://doi.org/10.1038/srep37340

    Article  CAS  Google Scholar 

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Correspondence to Mauricio Rodríguez-Dorantes .

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Rodríguez-Dorantes, M. et al. (2021). Prostate Cancer Spheroids: A Three-Dimensional Model for Studying Tumor Heterogeneity. In: Robles-Flores, M. (eds) Cancer Cell Signaling. Methods in Molecular Biology, vol 2174. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0759-6_2

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  • DOI: https://doi.org/10.1007/978-1-0716-0759-6_2

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-0758-9

  • Online ISBN: 978-1-0716-0759-6

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