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Models of Prostate Cancer Bone Metastasis

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Bone Research Protocols

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1914))

Abstract

More than 80% of patients with advanced prostate cancer (PCa) experience bone metastasis, which negatively impacts overall survival and patient quality of life. Various mouse models have been used to study the mechanisms of bone metastasis over the years; however, there is currently no model that fully recapitulates what happens in humans because bone metastasis rarely occurs in spontaneous PCa mouse models. Nevertheless, animal models of bone metastasis using several different tumor inoculation routes have been developed to help study bone metastatic progression, which occurs particularly in late-stage PCa patients. This chapter describes the protocols commonly used to develop models of bone metastatic cancer in mice using different percutaneous injection methods (Intracardiac and Intraosseous). These models are useful for understanding the molecular mechanisms of bone metastatic progression, including tumor tissue tropism and tumor growth within the bone marrow microenvironment. Better understanding of the mechanisms involved in these processes will clearly lead to the development of new therapeutic strategies for PCa patients with bone metastases.

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References

  1. Saad F, Olsson C, Schulman CC (2004) Skeletal morbidity in men with prostate cancer: quality-of-life considerations throughout the continuum of care. Eur Urol 46(6):731–739; discussion 739-740. https://doi.org/10.1016/j.eururo.2004.08.016

    Article  PubMed  Google Scholar 

  2. Bubendorf L, Schopfer A, Wagner U, Sauter G, Moch H, Willi N, Gasser TC, Mihatsch MJ (2000) Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. Hum Pathol 31(5):578–583

    Article  CAS  PubMed  Google Scholar 

  3. Pettaway CA, Pathak S, Greene G, Ramirez E, Wilson MR, Killion JJ, Fidler IJ (1996) Selection of highly metastatic variants of different human prostatic carcinomas using orthotopic implantation in nude mice. Clin Cancer Res 2(9):1627–1636

    CAS  PubMed  Google Scholar 

  4. Gingrich JR, Barrios RJ, Morton RA, Boyce BF, DeMayo FJ, Finegold MJ, Angelopoulou R, Rosen JM, Greenberg NM (1996) Metastatic prostate cancer in a transgenic mouse. Cancer Res 56(18):4096–4102

    CAS  PubMed  Google Scholar 

  5. Thalmann GN, Anezinis PE, Chang SM, Zhau HE, Kim EE, Hopwood VL, Pathak S, von Eschenbach AC, Chung LW (1994) Androgen-independent cancer progression and bone metastasis in the LNCaP model of human prostate cancer. Cancer Res 54(10):2577–2581

    CAS  PubMed  Google Scholar 

  6. Hurwitz AA, Foster BA, Allison JP, Greenberg NM, Kwon ED (2001) The TRAMP mouse as a model for prostate cancer. Curr Protoc Immunol Chapter 20:Unit 20 25. https://doi.org/10.1002/0471142735.im2005s45

  7. Wang S, Gao J, Lei Q, Rozengurt N, Pritchard C, Jiao J, Thomas GV, Li G, Roy-Burman P, Nelson PS, Liu X, Wu H (2003) Prostate-specific deletion of the murine Pten tumor suppressor gene leads to metastatic prostate cancer. Cancer Cell 4(3):209–221

    Article  CAS  PubMed  Google Scholar 

  8. An Z, Wang X, Geller J, Moossa AR, Hoffman RM (1998) Surgical orthotopic implantation allows high lung and lymph node metastatic expression of human prostate carcinoma cell line PC-3 in nude mice. Prostate 34(3):169–174

    Article  CAS  PubMed  Google Scholar 

  9. Kalikin LM, Schneider A, Thakur MA, Fridman Y, Griffin LB, Dunn RL, Rosol TJ, Shah RB, Rehemtulla A, McCauley LK, Pienta KJ (2003) In vivo visualization of metastatic prostate cancer and quantitation of disease progression in immunocompromised mice. Cancer Biol Ther 2(6):656–660

    Article  PubMed  Google Scholar 

  10. Drake JM, Gabriel CL, Henry MD (2005) Assessing tumor growth and distribution in a model of prostate cancer metastasis using bioluminescence imaging. Clin Exp Metastasis 22(8):674–684. https://doi.org/10.1007/s10585-006-9011-4

    Article  PubMed  Google Scholar 

  11. Arguello F, Baggs RB, Frantz CN (1988) A murine model of experimental metastasis to bone and bone marrow. Cancer Res 48(23):6876–6881

    CAS  PubMed  Google Scholar 

  12. Corey E, Quinn JE, Bladou F, Brown LG, Roudier MP, Brown JM, Buhler KR, Vessella RL (2002) Establishment and characterization of osseous prostate cancer models: intra-tibial injection of human prostate cancer cells. Prostate 52(1):20–33. https://doi.org/10.1002/pros.10091

    Article  PubMed  Google Scholar 

  13. Carceles-Cordon M, Rodriguez-Fernandez I, Rodriguez-Bravo V, Cordon-Cardo C, Domingo-Domenech J (2016) In vivo bioluminescence imaging of luciferase-labeled cancer cells. Bio-protocol 6(6). https://doi.org/10.21769/BioProtoc.1762

  14. Schneider A, Kalikin LM, Mattos AC, Keller ET, Allen MJ, Pienta KJ, McCauley LK (2005) Bone turnover mediates preferential localization of prostate cancer in the skeleton. Endocrinology 146(4):1727–1736. https://doi.org/10.1210/en.2004-1211

    Article  CAS  PubMed  Google Scholar 

  15. Wu TT, Sikes RA, Cui Q, Thalmann GN, Kao C, Murphy CF, Yang H, Zhau HE, Balian G, Chung LW (1998) Establishing human prostate cancer cell xenografts in bone: induction of osteoblastic reaction by prostate-specific antigen-producing tumors in athymic and SCID/bg mice using LNCaP and lineage-derived metastatic sublines. Int J Cancer 77(6):887–894

    Article  CAS  PubMed  Google Scholar 

  16. Nemeth JA, Harb JF, Barroso U Jr, He Z, Grignon DJ, Cher ML (1999) Severe combined immunodeficient-hu model of human prostate cancer metastasis to human bone. Cancer Res 59(8):1987–1993

    CAS  PubMed  Google Scholar 

  17. Kozlowski JM, Fidler IJ, Campbell D, Xu ZL, Kaighn ME, Hart IR (1984) Metastatic behavior of human tumor cell lines grown in the nude mouse. Cancer Res 44(8):3522–3529

    CAS  PubMed  Google Scholar 

  18. Morrissey C, Kostenuik PL, Brown LG, Vessella RL, Corey E (2007) Host-derived RANKL is responsible for osteolysis in a C4-2 human prostate cancer xenograft model of experimental bone metastases. BMC Cancer 7:148. https://doi.org/10.1186/1471-2407-7-148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hall CL, Bafico A, Dai J, Aaronson SA, Keller ET (2005) Prostate cancer cells promote osteoblastic bone metastases through Wnts. Cancer Res 65(17):7554–7560. https://doi.org/10.1158/0008-5472.CAN-05-1317

    Article  CAS  PubMed  Google Scholar 

  20. LeRoy BE, Thudi NK, Nadella MV, Toribio RE, Tannehill-Gregg SH, van Bokhoven A, Davis D, Corn S, Rosol TJ (2006) New bone formation and osteolysis by a metastatic, highly invasive canine prostate carcinoma xenograft. Prostate 66(11):1213–1222. https://doi.org/10.1002/pros.20408

    Article  CAS  PubMed  Google Scholar 

  21. McCabe NP, Madajka M, Vasanji A, Byzova TV (2008) Intraosseous injection of RM1 murine prostate cancer cells promotes rapid osteolysis and periosteal bone deposition. Clin Exp Metastasis 25(5):581–590. https://doi.org/10.1007/s10585-008-9175-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Power CA, Pwint H, Chan J, Cho J, Yu Y, Walsh W, Russell PJ (2009) A novel model of bone-metastatic prostate cancer in immunocompetent mice. Prostate 69(15):1613–1623. https://doi.org/10.1002/pros.21010

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

This work is directly supported by National Cancer Institute (CA163124, Y. Shiozawa), Department of Defense (W81XWH-14-1-0403 and W81XWH-17-1-0541, Y. Shiozawa), the Wake Forest Baptist Comprehensive Cancer Center Internal Pilot Funding (Y. Shiozawa), and the Wake Forest School of Medicine Internal Clinical and Translational Science Institute Pilot Funding (Y. Shiozawa). Y Shiozawa is supported as the Translational Research Academy which is supported by the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, through Grant Award Number UL1TR001420. This work is also supported by the National Cancer Institute’s Cancer Center Support Grant award number P30CA012197 issued to the Wake Forest Baptist Comprehensive Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Department of Cancer Biology and Wake Forest Baptist Comprehensive Cancer Center, Wake Forest University Health Sciences, Winston-Salem, NC, USA

    Sun Hee Park, Matthew Robert Eber & Yusuke Shiozawa

Authors
  1. Sun Hee Park
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  2. Matthew Robert Eber
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  3. Yusuke Shiozawa
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Correspondence to Yusuke Shiozawa .

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Editors and Affiliations

  1. Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK

    Aymen I. Idris

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Park, S.H., Eber, M.R., Shiozawa, Y. (2019). Models of Prostate Cancer Bone Metastasis. In: Idris, A. (eds) Bone Research Protocols. Methods in Molecular Biology, vol 1914. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8997-3_16

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  • DOI: https://doi.org/10.1007/978-1-4939-8997-3_16

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-8996-6

  • Online ISBN: 978-1-4939-8997-3

  • eBook Packages: Springer Protocols

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