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Animal Models for Bone Metastasis Study

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Handbook of Animal Models and its Uses in Cancer Research

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Abstract

Cancer-mediated death is promoted by the process of metastasis. Often, bone is the preferred site of metastasis. The process of metastasis at the bone is mediated by interactions between cancer cells and bone marrow which results in production of factors that promote proliferation and survival. Investigations carried out to study these interactions pointed out that tumor cells in bone marrow can remain dormant for an undefined period of time lasting up to months and years. At the end of this stage, the cancer cells become active and form metastases. There is a need to understand these mechanisms on a real-time basis. In order to accomplish this, animal models of bone metastasis are used. The animal models used for investigation of bone metastasis need to be clinically suitable to mimic the events that occur in human bone metastasis. The results obtained from these model organisms also need to be consistent, so that these results can be used for designing therapeutic regimes. Use of model organisms also gives us the benefit of determining the toxicity profile of the therapeutic agents.

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References

  • Amundson E et al (2005) A novel intravertebral tumor model in rabbits. Neurosurgery 57(2):341–346; discussion 341–6

    Article  Google Scholar 

  • Anidjar M et al (2012) Refining the orthotopic dog prostate cancer (DPC)-1 model to better bridge the gap between rodents and men. Prostate 72(7):752–761

    Article  CAS  Google Scholar 

  • 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  Google Scholar 

  • Baron R, Ferrari S, Russell RG (2011) Denosumab and bisphosphonates: different mechanisms of action and effects. Bone 48(4):677–692

    Article  CAS  Google Scholar 

  • Bellanger A et al (2017) The critical role of the ZNF217 oncogene in promoting breast cancer metastasis to the bone. J Pathol 242(1):73–89

    Article  CAS  Google Scholar 

  • Berenson JR (2005) Recommendations for zoledronic acid treatment of patients with bone metastases. Oncologist 10(1):52–62

    Article  CAS  Google Scholar 

  • Biswas S et al (2011) Anti-transforming growth factor ß antibody treatment rescues bone loss and prevents breast cancer metastasis to bone. PLoS One 6(11):e27090

    Article  CAS  Google Scholar 

  • Body JJ et al (2004) Oral ibandronate reduces the risk of skeletal complications in breast cancer patients with metastatic bone disease: results from two randomised, placebo-controlled phase III studies. Br J Cancer 90(6):1133–1137

    Article  CAS  Google Scholar 

  • Cao R et al (2008) Structures of a potent phenylalkyl bisphosphonate inhibitor bound to farnesyl and geranylgeranyl diphosphate synthases. Proteins 73(2):431–439

    Article  CAS  Google Scholar 

  • Chen D, Zhao M, Mundy GR (2004) Bone morphogenetic proteins. Growth Factors 22(4):233–241

    Article  CAS  Google Scholar 

  • Chen G, Deng C, Li YP (2012) TGF-β and BMP signaling in osteoblast differentiation and bone formation. Int J Biol Sci 8(2):272–288

    Article  CAS  Google Scholar 

  • Chiang PH et al (2013) Zoledronic acid treatment for cancerous bone metastases: a phase IV study in Taiwan. J Cancer Res Ther 9(4):653–659

    Article  CAS  Google Scholar 

  • Choi JA et al (2008) Evolution of VX2 carcinoma in rabbit tibia: magnetic resonance imaging with pathologic correlation. Clin Imaging 32(2):128–135

    Article  Google Scholar 

  • Chowdhury K et al (2017) Simvastatin and MBCD inhibit breast cancer-induced osteoclast activity by targeting osteoclastogenic factors. Cancer Investig 35(6):403–413

    Article  CAS  Google Scholar 

  • Chu T et al (2014) Lung cancer-derived Dickkopf1 is associated with bone metastasis and the mechanism involves the inhibition of osteoblast differentiation. Biochem Biophys Res Commun 443(3):962–968

    Article  CAS  Google Scholar 

  • Coleman RE (2001) Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev 27(3):165–176

    Article  CAS  Google Scholar 

  • Coleman RE (2006) Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res 12(20 Pt 2):6243s–6249s

    Article  Google Scholar 

  • Coleman RE et al (2020) Bone metastases. Nat Rev Dis Primers 6(1):83

    Article  Google Scholar 

  • Coniglio SJ (2018) Role of tumor-derived chemokines in osteolytic bone metastasis. Front Endocrinol (Lausanne) 9:313

    Article  Google Scholar 

  • Cossigny D, Quan GM (2012) In vivo animal models of spinal metastasis. Cancer Metastasis Rev 31(1–2):99–108

    Article  Google Scholar 

  • Coukell AJ, Markham A (1998) Pamidronate. A review of its use in the management of osteolytic bone metastases, tumour-induced hypercalcaemia and Paget’s disease of bone. Drugs Aging 12(2):149–168

    Article  CAS  Google Scholar 

  • Croucher PI et al (2001) Osteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma. Blood 98(13):3534–3540

    Article  CAS  Google Scholar 

  • Croucher PI, McDonald MM, Martin TJ (2016) Bone metastasis: the importance of the neighbourhood. Nat Rev Cancer 16(6):373–386

    Article  CAS  Google Scholar 

  • Di L et al (2019) Discovery of a natural small-molecule compound that suppresses tumor EMT, stemness and metastasis by inhibiting TGFβ/BMP signaling in triple-negative breast cancer. J Exp Clin Cancer Res 38(1):134

    Article  Google Scholar 

  • Diel IJ (2010) Bisphosphonates in breast cancer patients with bone metastases. Breast Care (Basel) 5(5):306–311

    Article  Google Scholar 

  • Dionísio MR et al (2019) Clinical and translational pharmacology of drugs for the prevention and treatment of bone metastases and cancer-induced bone loss. Br J Clin Pharmacol 85(6):1114–1124

    Article  Google Scholar 

  • Ducy P et al (2000) Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell 100(2):197–207

    Article  CAS  Google Scholar 

  • Dudley AC et al (2008) Calcification of multipotent prostate tumor endothelium. Cancer Cell 14(3):201–211

    Article  CAS  Google Scholar 

  • Ferreira S, Dormehl I, Botelho MF (2012) Radiopharmaceuticals for bone metastasis therapy and beyond: a voyage from the past to the present and a look to the future. Cancer Biother Radiopharm 27(9):535–551

    CAS  Google Scholar 

  • Fulfaro F et al (1998) The role of bisphosphonates in the treatment of painful metastatic bone disease: a review of phase III trials. Pain 78(3):157–169

    Article  CAS  Google Scholar 

  • Goblirsch M et al (2004) Radiation treatment decreases bone cancer pain, osteolysis and tumor size. Radiat Res 161(2):228–234

    Article  CAS  Google Scholar 

  • Hernández I et al (2010) Novel alternatively spliced ADAM8 isoforms contribute to the aggressive bone metastatic phenotype of lung cancer. Oncogene 29(26):3758–3769

    Article  Google Scholar 

  • Hortobagyi GN et al (1996) Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bone metastases. Protocol 19 Aredia Breast Cancer Study Group. N Engl J Med 335(24):1785–1791

    Article  CAS  Google Scholar 

  • Ip C (1996) Mammary tumorigenesis and chemoprevention studies in carcinogen-treated rats. J Mammary Gland Biol Neoplasia 1(1):37–47

    Article  CAS  Google Scholar 

  • Jang BS (2013) MicroSPECT and MicroPET imaging of small animals for drug development. Toxicol Res 29(1):1–6

    Article  CAS  Google Scholar 

  • Johnstone C, Lutz ST (2014) External beam radiotherapy and bone metastases. In: Bone metastases. Springer, Dordrecht, pp 175–185

    Chapter  Google Scholar 

  • Kang EJ et al (2017) Liensinine and Nuciferine, bioactive components of Nelumbo nucifera, inhibit the growth of breast cancer cells and breast cancer-associated bone loss. Evid Based Complement Altern Med 2017:1583185

    Article  Google Scholar 

  • Karam JA et al (2003) Molecular imaging in prostate cancer. J Cell Biochem 90(3):473–483

    Article  CAS  Google Scholar 

  • Kenkre JS, Bassett J (2018) The bone remodelling cycle. Ann Clin Biochem 55(3):308–327

    Article  CAS  Google Scholar 

  • Khoo WH et al (2019) A niche-dependent myeloid transcriptome signature defines dormant myeloma cells. Blood 134(1):30–43

    Article  CAS  Google Scholar 

  • Koba W, Jelicks LA, Fine EJ (2013) MicroPET/SPECT/CT imaging of small animal models of disease. Am J Pathol 182(2):319–324

    Article  CAS  Google Scholar 

  • Koga T et al (2005) NFAT and Osterix cooperatively regulate bone formation. Nat Med 11(8):880–885

    Article  CAS  Google Scholar 

  • Lang J et al (2018) Bone turnover markers and novel biomarkers in lung cancer bone metastases. Biomarkers 23(6):518–526

    Article  CAS  Google Scholar 

  • Lawson MA et al (2015) Osteoclasts control reactivation of dormant myeloma cells by remodelling the endosteal niche. Nat Commun 6:8983

    Article  CAS  Google Scholar 

  • Lefley D et al (2019) Development of clinically relevant in vivo metastasis models using human bone discs and breast cancer patient-derived xenografts. Breast Cancer Res 21(1):130

    Article  CAS  Google Scholar 

  • Lelekakis M et al (1999) A novel orthotopic model of breast cancer metastasis to bone. Clin Exp Metastasis 17(2):163–170

    Article  CAS  Google Scholar 

  • Lin SC et al (2017) Endothelial-to-osteoblast conversion generates osteoblastic metastasis of prostate cancer. Dev Cell 41(5):467–480.e3

    Article  CAS  Google Scholar 

  • Maini CL et al (2004) 153Sm-EDTMP for bone pain palliation in skeletal metastases. Eur J Nucl Med Mol Imaging 31(Suppl 1):S171–S178

    Article  Google Scholar 

  • Mandal CC (2015) High cholesterol deteriorates bone health: new insights into molecular mechanisms. Front Endocrinol (Lausanne) 6:165

    Article  Google Scholar 

  • Mandal CC (2020) Osteolytic metastasis in breast cancer: effective prevention strategies. Expert Rev Anticancer Ther 20(9):797–811

    Article  CAS  Google Scholar 

  • Mandal CC, Ghosh Choudhury G, Ghosh-Choudhury N (2009) Phosphatidylinositol 3 kinase/Akt signal relay cooperates with smad in bone morphogenetic protein-2-induced colony stimulating factor-1 (CSF-1) expression and osteoclast differentiation. Endocrinology 150(11):4989–4998

    Article  CAS  Google Scholar 

  • Mandal CC et al (2010) Integration of phosphatidylinositol 3-kinase, Akt kinase, and Smad signaling pathway in BMP-2-induced osterix expression. Calcif Tissue Int 87(6):533–540

    Article  CAS  Google Scholar 

  • Mandal CC et al (2011) Reactive oxygen species derived from Nox4 mediate BMP2 gene transcription and osteoblast differentiation. Biochem J 433(2):393–402

    Article  CAS  Google Scholar 

  • Mandal CC et al (2016) Bone morphogenetic protein-2 (BMP-2) activates NFATc1 transcription factor via an autoregulatory loop involving Smad/Akt/Ca2+ signaling. J Biol Chem 291(3):1148–1161

    Article  CAS  Google Scholar 

  • Mizutani R, Suzuki Y (2012) X-ray microtomography in biology. Micron 43(2–3):104–115

    Article  Google Scholar 

  • Morony S et al (2001) Osteoprotegerin inhibits osteolysis and decreases skeletal tumor burden in syngeneic and nude mouse models of experimental bone metastasis. Cancer Res 61(11):4432–4436

    CAS  Google Scholar 

  • Nielsen OS (1999) Palliative radiotherapy of bone metastases: there is now evidence for the use of single fractions. Radiother Oncol 52(2):95–96

    CAS  Google Scholar 

  • Obeid M et al (2018) Translational animal models for liver cancer. Am J Intervent Radiol 2(2):1–7

    Google Scholar 

  • Pang H et al (2017) The biological effects of Dickkopf1 on small cell lung cancer cells and bone metastasis. Oncol Res 25(1):35–42

    Article  Google Scholar 

  • Papapetrou PD (2009) Bisphosphonate-associated adverse events. Hormones (Athens) 8(2):96–110

    Article  Google Scholar 

  • Passineau MJ et al (2005) The natural history of a novel, systemic, disseminated model of syngeneic mouse B-cell lymphoma. Leuk Lymphoma 46(11):1627–1638

    Article  Google Scholar 

  • Pearse RN et al (2001) Multiple myeloma disrupts the TRANCE/ osteoprotegerin cytokine axis to trigger bone destruction and promote tumor progression. Proc Natl Acad Sci U S A 98(20):11581–11586

    Article  CAS  Google Scholar 

  • Pore SK et al (2018) Prevention of breast cancer-induced osteolytic bone resorption by benzyl isothiocyanate. Carcinogenesis 39(2):134–145

    Article  CAS  Google Scholar 

  • Räikkönen J et al (2009) Zoledronic acid induces formation of a pro-apoptotic ATP analogue and isopentenyl pyrophosphate in osteoclasts in vivo and in MCF-7 cells in vitro. Br J Pharmacol 157(3):427–435

    Article  Google Scholar 

  • Resche I et al (1997) A dose-controlled study of 153Sm-ethylenediaminetetramethylenephosphonate (EDTMP) in the treatment of patients with painful bone metastases. Eur J Cancer 33(10):1583–1591

    Article  CAS  Google Scholar 

  • Rogers MJ et al (1999) Molecular mechanisms of action of bisphosphonates. Bone 24(5 Suppl):73s–79s

    Article  CAS  Google Scholar 

  • Rosen LS et al (2001) Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind, comparative trial. Cancer J 7(5):377–387

    CAS  Google Scholar 

  • Rosol TJ et al (2003) Animal models of bone metastasis. Cancer 97(3 Suppl):748–757

    Article  Google Scholar 

  • Schubert A et al (2011) Agonists and antagonists of GnRH-I and -II reduce metastasis formation by triple-negative human breast cancer cells in vivo. Breast Cancer Res Treat 130(3):783–790

    Article  CAS  Google Scholar 

  • Seely J, Boorman GA (1999) Mammary gland and specialized sebaceous glands (Zymbal, preputial, clitoral, anal). In: Pathology of the mouse: reference and atlas. Cache River Press, Vienna, p 699

    Google Scholar 

  • Selvaggi G, Scagliotti GV (2005) Management of bone metastases in cancer: a review. Crit Rev Oncol/Hematol 56(3):365–378

    Article  Google Scholar 

  • Sethi N et al (2011) Tumor-derived JAGGED1 promotes osteolytic bone metastasis of breast cancer by engaging notch signaling in bone cells. Cancer Cell 19(2):192–205

    Article  CAS  Google Scholar 

  • Sharma T et al (2016) A molecular view of pathological microcalcification in breast cancer. J Mammary Gland Biol Neoplasia 21(1–2):25–40

    Article  Google Scholar 

  • Sharma A et al (2019) Metformin exhibited anticancer activity by lowering cellular cholesterol content in breast cancer cells. PLoS One 14(1):e0209435

    Article  CAS  Google Scholar 

  • Sharma T et al (2020) Docosahexaenoic acid (DHA) inhibits bone morphogenetic protein-2 (BMP-2) elevated osteoblast potential of metastatic breast cancer (MDA-MB-231) cells in mammary microcalcification. Nutr Cancer 72(5):873–883

    Article  CAS  Google Scholar 

  • Shiozawa Y, Pienta KJ, Taichman RS (2011) Hematopoietic stem cell niche is a potential therapeutic target for bone metastatic tumors. Clin Cancer Res 17(17):5553–5558

    Article  CAS  Google Scholar 

  • Simmons JK et al (2015) Animal models of bone metastasis. Vet Pathol 52(5):827–841

    Article  CAS  Google Scholar 

  • Singh AS, Figg WD (2005) In vivo models of prostate cancer metastasis to bone. J Urol 174(3):820–826

    Article  Google Scholar 

  • Small EJ et al (2003) Combined analysis of two multicenter, randomized, placebo-controlled studies of pamidronate disodium for the palliation of bone pain in men with metastatic prostate cancer. J Clin Oncol 21(23):4277–4284

    Article  CAS  Google Scholar 

  • Soodgupta D et al (2013) Very late antigen-4 (α(4)β(1) Integrin) targeted PET imaging of multiple myeloma. PLoS One 8(2):e55841

    Article  CAS  Google Scholar 

  • Steger GG, Bartsch R (2011) Denosumab for the treatment of bone metastases in breast cancer: evidence and opinion. Ther Adv Med Oncol 3(5):233–243

    Article  CAS  Google Scholar 

  • Stoica G, Koestner A, Capen CC (1984) Neoplasms induced with high single doses of N-ethyl-N-nitrosourea in 30-day-old Sprague-Dawley rats, with special emphasis on mammary neoplasia. Anticancer Res 4(1–2):5–12

    CAS  Google Scholar 

  • Stopeck AT et al (2010) Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. J Clin Oncol 28(35):5132–5139

    Article  CAS  Google Scholar 

  • Taghian A et al (1993) Quantitative comparison between the transplantability of human and murine tumors into the subcutaneous tissue of NCr/Sed-nu/nu nude and severe combined immunodeficient mice. Cancer Res 53(20):5012–5017

    CAS  Google Scholar 

  • Tatsui CE et al (2009) An orthotopic murine model of human spinal metastasis: histological and functional correlations. J Neurosurg Spine 10(6):501–512

    Article  Google Scholar 

  • Terpos E et al (2003) Soluble receptor activator of nuclear factor kappaB ligand-osteoprotegerin ratio predicts survival in multiple myeloma: proposal for a novel prognostic index. Blood 102(3):1064–1069

    Article  CAS  Google Scholar 

  • Theriault RL et al (1999) Pamidronate reduces skeletal morbidity in women with advanced breast cancer and lytic bone lesions: a randomized, placebo-controlled trial. Protocol 18 Aredia Breast Cancer Study Group. J Clin Oncol 17(3):846–854

    Article  CAS  Google Scholar 

  • van der Linde-Sipman JS, van den Ingh TS (2000) Primary and metastatic carcinomas in the digits of cats. Vet Q 22(3):141–145

    Article  Google Scholar 

  • Vicent S et al (2008) A novel lung cancer signature mediates metastatic bone colonization by a dual mechanism. Cancer Res 68(7):2275–2285

    Article  CAS  Google Scholar 

  • von Moos R et al (2019) Management of bone health in solid tumours: from bisphosphonates to a monoclonal antibody. Cancer Treat Rev 76:57–67

    Article  Google Scholar 

  • Wan X et al (2014) Prostate cancer cell-stromal cell crosstalk via FGFR1 mediates antitumor activity of dovitinib in bone metastases. Sci Transl Med 6(252):252ra122

    Article  Google Scholar 

  • Wang S et al (2019a) FOXF2 reprograms breast cancer cells into bone metastasis seeds. Nat Commun 10(1):2707

    Article  Google Scholar 

  • Wang L et al (2019b) Pitavastatin slows tumor progression and alters urine-derived volatile organic compounds through the mevalonate pathway. FASEB J 33(12):13710–13721

    Article  CAS  Google Scholar 

  • Wetterwald A et al (2002) Optical imaging of cancer metastasis to bone marrow: a mouse model of minimal residual disease. Am J Pathol 160(3):1143–1153

    Article  Google Scholar 

  • Wright LE et al (2013) Curcuminoids block TGF-β signaling in human breast cancer cells and limit osteolysis in a murine model of breast cancer bone metastasis. J Nat Prod 76(3):316–321

    Article  CAS  Google Scholar 

  • Yamaguchi M et al (2014) Curcumin analogue UBS109 prevents bone loss in breast cancer bone metastasis mouse model: involvement in osteoblastogenesis and osteoclastogenesis. Cell Tissue Res 357(1):245–252

    Article  CAS  Google Scholar 

  • Zhang K et al (2019) Application of hydroxyapatite nanoparticles in tumor-associated bone segmental defect. Sci Adv 5(8):eaax6946

    Article  CAS  Google Scholar 

  • Zheleznyak A et al (2012) Integrin α(v)β3 as a PET imaging biomarker for osteoclast number in mouse models of negative and positive osteoclast regulation. Mol Imaging Biol 14(4):500–508

    Article  Google Scholar 

  • Zuo C et al (2012) Osteoblastogenesis regulation signals in bone remodeling. Osteoporos Int 23(6):1653–1663

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, Ajmer, Rajasthan, India

    Manas K. Mahapatra & Chandi C. Mandal

Authors
  1. Manas K. Mahapatra
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  2. Chandi C. Mandal
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Correspondence to Chandi C. Mandal .

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Editors and Affiliations

  1. Cancer Biology and Biotechnology Lab Faculty of Allied Health Sciences Chettinad Hospital & Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India

    Surajit Pathak

  2. Cancer Biology and Biotechnology Lab Faculty of Allied Health Sciences Chettinad Hospital & Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India

    Antara Banerjee

  3. AGENTEM (Adana Genetic Diseases Diagnosis and Treatment Center) & Medical Genetics Department of Medical Faculty, Cukurova University, Adana, Turkey

    Atil Bisgin

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Mahapatra, M.K., Mandal, C.C. (2023). Animal Models for Bone Metastasis Study. In: Pathak, S., Banerjee, A., Bisgin, A. (eds) Handbook of Animal Models and its Uses in Cancer Research. Springer, Singapore. https://doi.org/10.1007/978-981-19-3824-5_15

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