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Transplantable Animal Studies and Whole-Body Optical Imaging in Prostate Carcinoma

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Prostate Cancer

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1786))

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Abstract

Current treatments of advanced prostate cancer only marginally increase overall survival and can be regarded as predominantly palliative. Hence, there is an urgent need for novel therapeutic strategies for the treatment of primary tumors and, more importantly perhaps, for the prevention of tumor progression and metastasis formation. Clinically relevant preclinical models are therefore urgently needed. An ideal, clinically relevant preclinical model would mimic the genetic and phenotypic changes that occur at the different stages of human prostate cancer progression and subsequent metastasis. In this chapter, transplantable xenograft prostate cancer models are described, in which human prostate cancer cells are transplanted into host animals (e.g., immune-deficient mice). Cancer cells can be administered to the small laboratory animals in various ways, including inoculation of the prostate tumor cells subcutaneously, at the anatomical site of origin (orthotopically), or at the metastatic site. In addition, we describe imaging methods suitable for small laboratory animals with emphasis on optical imaging (bioluminescence and fluorescence).

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References

  1. Bastian PJ, Carter BH, Bjartell A, Seitz M, Stanislaus P, Montorsi F, Stief CG, Schroder F (2009) Insignificant prostate cancer and active surveillance: from definition to clinical implications. Eur Urol 55:1321–1330

    Article  PubMed  Google Scholar 

  2. Heidenreich A, Bastian PJ, Bellmunt J et al (2014) EAU guidelines on prostate cancer. Part II: treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol 65:467–479

    Article  CAS  PubMed  Google Scholar 

  3. van der Horst G, van der Pluijm G (2012) Preclinical models that illuminate the bone metastasis cascade. Recent Results Cancer Res 192:1–31

    Article  CAS  PubMed  Google Scholar 

  4. van der Horst G, van der Pluijm G (2012) Preclinical imaging of the cellular and molecular events in the multistep process of bone metastasis. Future Oncol 8:415–430

    Article  CAS  PubMed  Google Scholar 

  5. Khanna C, Hunter K (2005) Modeling metastasis in vivo. Carcinogenesis 26:513–523

    Article  CAS  PubMed  Google Scholar 

  6. Buijs JT, Rentsch CA, van der Horst G et al (2007) BMP7, a putative regulator of epithelial homeostasis in the human prostate, is a potent inhibitor of prostate cancer bone metastasis in vivo. Am J Pathol 171:1047–1057

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Buijs JT, van der Pluijm G (2009) Osteotropic cancers: from primary tumor to bone. Cancer Lett 273:177–193

    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 34:169–174

    Article  CAS  PubMed  Google Scholar 

  9. Schwaninger R, Rentsch CA, Wetterwald A et al (2007) Lack of noggin expression by cancer cells is a determinant of the osteoblast response in bone metastases. Am J Pathol 170:160–175

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Lynch CC, Hikosaka A, Acuff HB et al (2005) MMP-7 promotes prostate cancer-induced osteolysis via the solubilization of RANKL. Cancer Cell 7:485–496

    Article  CAS  PubMed  Google Scholar 

  11. Nannuru KC, Futakuchi M, Varney ML, Vincent TM, Marcusson EG, Singh RK (2010) Matrix metalloproteinase (MMP)-13 regulates mammary tumor-induced osteolysis by activating MMP9 and transforming growth factor-beta signaling at the tumor-bone interface. Cancer Res 70:3494–3504

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Wang N, Docherty FE, Brown HK et al (2014) Prostate cancer cells preferentially home to osteoblast-rich areas in the early stages of bone metastasis: evidence from in vivo models. J Bone Miner Res 29:2688–2696

    Article  CAS  PubMed  Google Scholar 

  13. Yu C, Shiozawa Y, Taichman RS, McCauley LK, Pienta K, Keller E (2012) Prostate cancer and parasitism of the bone hematopoietic stem cell niche. Crit Rev Eukaryot Gene Expr 22:131–148

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Buijs JT, Henriquez NV, van Overveld PG et al (2007) Bone morphogenetic protein 7 in the development and treatment of bone metastases from breast cancer. Cancer Res 67:8742–8751

    Article  CAS  PubMed  Google Scholar 

  15. van der Horst G, van den Hoogen C, Buijs JT et al (2011) Targeting of alpha(v)-integrins in stem/progenitor cells and supportive microenvironment impairs bone metastasis in human prostate cancer. Neoplasia 13:516–525

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. van der Pluijm G, Sijmons B, Vloedgraven H, Deckers M, Papapoulos S, Lowik C (2001) Monitoring metastatic behavior of human tumor cells in mice with species-specific polymerase chain reaction: elevated expression of angiogenesis and bone resorption stimulators by breast cancer in bone metastases. J Bone Miner Res 16:1077–1091

    Article  PubMed  Google Scholar 

  17. van der Pluijm G, Que I, Sijmons B, Buijs JT, Lowik CW, Wetterwald A, Thalmann GN, Papapoulos SE, Cecchini MG (2005) Interference with the microenvironmental support impairs the de novo formation of bone metastases in vivo. Cancer Res 65:7682–7690

    Article  PubMed  Google Scholar 

  18. Peyruchaud O, Serre CM, NicAmhlaoibh R, Fournier P, Clezardin P (2003) Angiostatin inhibits bone metastasis formation in nude mice through a direct anti-osteoclastic activity. J Biol Chem 278:45826–45832

    Article  CAS  PubMed  Google Scholar 

  19. van den Hoogen C, van der Horst G, Cheung H et al (2010) High aldehyde dehydrogenase activity identifies tumor-initiating and metastasis-initiating cells in human prostate cancer. Cancer Res 70:5163–5173

    Article  CAS  PubMed  Google Scholar 

  20. van den Hoogen C, van der Horst G, Cheung H, Buijs JT, Pelger RC, van der Pluijm G (2011) The aldehyde dehydrogenase enzyme 7A1 is functionally involved in prostate cancer bone metastasis. Clin Exp Metastasis 28:615–625

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. van den Hoogen C, van der Horst G, Cheung H, Buijs JT, Pelger RC, van der Pluijm G (2011) Integrin alphav expression is required for the acquisition of a metastatic stem/progenitor cell phenotype in human prostate cancer. Am J Pathol 179:2559–2568

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Kaijzel EL, van der Pluijm G, Lowik CW (2007) Whole-body optical imaging in animal models to assess cancer development and progression. Clin Cancer Res 13:3490–3497

    Article  PubMed  Google Scholar 

  23. Black PC, Shetty A, Brown GA, Esparza-Coss E, Metwalli AR, Agarwal PK, McConkey DJ, Hazle JD, Dinney CP (2010) Validating bladder cancer xenograft bioluminescence with magnetic resonance imaging: the significance of hypoxia and necrosis. BJU Int 106:1799–1804

    Article  PubMed  Google Scholar 

  24. Conway JR, Carragher NO, Timpson P (2014) Developments in preclinical cancer imaging: innovating the discovery of therapeutics. Nat Rev Cancer 14:314–328

    Article  CAS  PubMed  Google Scholar 

  25. Graves EE, Weissleder R, Ntziachristos V (2004) Fluorescence molecular imaging of small animal tumor models. Curr Mol Med 4:419–430

    Article  CAS  PubMed  Google Scholar 

  26. Teschendorf C, Warrington KH Jr, Siemann DW, Muzyczka N (2002) Comparison of the EF-1 alpha and the CMV promoter for engineering stable tumor cell lines using recombinant adeno-associated virus. Anticancer Res 22:3325–3330

    PubMed  CAS  Google Scholar 

  27. Klerk CP, Overmeer RM, Niers TM, Versteeg HH, Richel DJ, Buckle T, Van Noorden CJ, van Tellingen O (2007) Validity of bioluminescence measurements for noninvasive in vivo imaging of tumor load in small animals. BioTechniques 43(7–13):30

    Google Scholar 

  28. Stacer AC, Nyati S, Moudgil P, Iyengar R, Luker KE, Rehemtulla A, Luker GD (2013) NanoLuc reporter for dual luciferase imaging in living animals. Mol Imaging 12:1–13

    Article  CAS  PubMed  Google Scholar 

  29. Chung E, Yamashita H, Au P, Tannous BA, Fukumura D, Jain RK (2009) Secreted Gaussia luciferase as a biomarker for monitoring tumor progression and treatment response of systemic metastases. PLoS One 4:e8316

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Henriquez NV, van Overveld PG, Que I, Buijs JT, Bachelier R, Kaijzel EL, Lowik CW, Clezardin P, van der Pluijm G (2007) Advances in optical imaging and novel model systems for cancer metastasis research. Clin Exp Metastasis 24:699–705

    Article  PubMed  Google Scholar 

  31. Mezzanotte L, Que I, Kaijzel E, Branchini B, Roda A, Lowik C (2011) Sensitive dual color in vivo bioluminescence imaging using a new red codon optimized firefly luciferase and a green click beetle luciferase. PLoS One 6:e19277

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Deroose CM, De A, Loening AM, Chow PL, Ray P, Chatziioannou AF, Gambhir SS (2007) Multimodality imaging of tumor xenografts and metastases in mice with combined small-animal PET, small-animal CT, and bioluminescence imaging. J Nucl Med 48:295–303

    PubMed  CAS  Google Scholar 

  33. van der Horst G, van Asten JJ, Figdor A, van den Hoogen C, Cheung H, Bevers RF, Pelger RC, van der Pluijm G (2011) Real-time cancer cell tracking by bioluminescence in a preclinical model of human bladder cancer growth and metastasis. Eur Urol 60:337–343

    Article  PubMed  Google Scholar 

  34. Hilderbrand SA, Weissleder R (2010) Near-infrared fluorescence: application to in vivo molecular imaging. Curr Opin Chem Biol 14:71–79

    Article  CAS  PubMed  Google Scholar 

  35. Reeves KJ, Hurrell JE, Cecchini M, van der Pluijm G, Down JM, Eaton CL, Hamdy F, Clement-Lacroix P, Brown NJ (2015) Prostate cancer cells home to bone using a novel in vivo model: modulation by the integrin antagonist GLPG0187. Int J Cancer 136:1731–1740

    Article  CAS  PubMed  Google Scholar 

  36. Parish CR (1999) Fluorescent dyes for lymphocyte migration and proliferation studies. Immunol Cell Biol 77:499–508

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Geertje van der Horst .

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van der Horst, G., van der Mark, M., Cheung, H., van der Pluijm, G. (2018). Transplantable Animal Studies and Whole-Body Optical Imaging in Prostate Carcinoma. In: Culig, Z. (eds) Prostate Cancer. Methods in Molecular Biology, vol 1786. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7845-8_5

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  • DOI: https://doi.org/10.1007/978-1-4939-7845-8_5

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7843-4

  • Online ISBN: 978-1-4939-7845-8

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