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Abstract
Bone is the most prevalent metastatic site for breast cancer affecting ~70% of patients with late-stage disease. Treatments for this condition currently focus on controlling disease progression and limiting tumour-induced damage to bone, thereby playing a valuable role in increasing quality of life. However, limited understanding of the interplay between tumour cells and their environment during bone metastasis has impeded the development of curative treatments. To unravel the complex genetic and phenotypic alterations that occur during this process, it would be helpful to have a model in which tumours develop spontaneously at the primary site, spread to bone, undergo a dormancy phase and then, after a fixed timeframe, become re-activated to form osteolytic/mixed lesions in the skeleton. Unlike humans, spontaneous metastasis of primary mammary tumours to bone is rare in mice and no syngeneic models of oestrogen receptor positive disease have been reported. As there is no single model that authentically reproduces all of the genetic and phenotypic changes representative of human bone metastasis, this review discusses the traditional and novel mouse models that are used to study bone metastasis from breast cancer. Additionally, this review focuses on advances that have been made towards making these models more closely related to human disease in an attempt to help researchers select the correct model(s) for their experimental needs with the aim of improving translational efficacy between the laboratory and the clinic.
Keywords
Breast cancer
/
bone metastasis
/
mouse models
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Penelope D. Ottewell, Michelle A. Lawson.
Advances in murine models of breast cancer bone disease.
Journal of Cancer Metastasis and Treatment, 2021, 7: 11 DOI:10.20517/2394-4722.2021.14
| [1] |
Salvador F,Gomis RR.From latency to overt bone metastasis in breast cancer: potential for treatment and prevention.J Pathol2019;249:6-18 PMCID:PMC6771808
|
| [2] |
George CN,Theodoulou E,Wilson C.Oestrogen and zoledronic acid driven changes to the bone and immune environments: Potential mechanisms underlying the differential anti-tumour effects of zoledronic acid in pre- and post-menopausal conditions.J Bone Oncol2020;25:100317 PMCID:PMC7516134
|
| [3] |
Ma L,Weinberg RA.Tumour invasion and metastasis initiated by microRNA-10b in breast cancer.Nature2007;449:682-8
|
| [4] |
Huang Q,Schrier M.The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis.Nat Cell Biol2008;10:202-10
|
| [5] |
Cox TR,Schoof EM.The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase.Nature2015;522:106-10 PMCID:PMC4961239
|
| [6] |
Tulotta C,Freeman K.Endogenous Production of IL1B by Breast Cancer Cells Drives Metastasis and Colonization of the Bone Microenvironment.Clin Cancer Res2019;25:2769-82
|
| [7] |
Massagué J.Metastatic colonization by circulating tumour cells.Nature2016;529:298-306 PMCID:PMC5029466
|
| [8] |
Weilbaecher KN,McCauley LK.Cancer to bone: a fatal attraction.Nat Rev Cancer2011;11:411-25 PMCID:PMC3666847
|
| [9] |
Hess KR,Buzdar AU.Estrogen Receptors and Distinct Patterns of Breast Cancer Relapse.Breast Cancer Res Treat2003;78:105-18
|
| [10] |
Goss PE.Does tumour dormancy offer a therapeutic target?.Nat Rev Cancer2010;10:871-7
|
| [11] |
Tahara RK,Theriault RL. Bone Metastasis of Breast Cancer. In: Ahmad A, editor. Breast Cancer Metastasis and Drug Resistance. Cham: Springer International Publishing; 2019. pp. 105-29.
|
| [12] |
Owen KL.Beyond the vicious cycle: The role of innate osteoimmunity, automimicry and tumor-inherent changes in dictating bone metastasis.Mol Immunol2019;110:57-68
|
| [13] |
Ottewell PD.The role of osteoblasts in bone metastasis.J Bone Oncol2016;5:124-7 PMCID:PMC5063217
|
| [14] |
Heilmann T,Roscher M.Dasatinib prevents skeletal metastasis of osteotropic MDA-MB-231 cells in a xenograft mouse model.Arch Gynecol Obstet2020;301:1493-502
|
| [15] |
Bellahcène A,Detry C,Clézardin P.Transcriptome analysis reveals an osteoblast-like phenotype for human osteotropic breast cancer cells.Breast Cancer Res Treat2007;101:135-48
|
| [16] |
Eyre R,Santiago-Gómez A.Microenvironmental IL1β promotes breast cancer metastatic colonisation in the bone via activation of Wnt signalling.Nat Commun2019;10:5016 PMCID:PMC6825219
|
| [17] |
Tulotta C,Snaar-jagalska BE. Animal Models of Breast Cancer Bone Metastasis. In: Idris AI, editor. Bone Research Protocols. New York: Springer; 2019. pp. 309-30.
|
| [18] |
Ottewell PD,Mönkkönen H.Differential effect of doxorubicin and zoledronic acid on intraosseous versus extraosseous breast tumor growth in vivo.Clin Cancer Res2008;14:4658-66
|
| [19] |
Nutter F,Brown HK.Different molecular profiles are associated with breast cancer cell homing compared with colonisation of bone: evidence using a novel bone-seeking cell line.Endocr Relat Cancer2014;21:327-41
|
| [20] |
Reed ND.Long-term maintenance of normal human skin on congenitally athymic (nude) mice.Proc Soc Exp Biol Med1973;143:350-3
|
| [21] |
Zhang X.Establishment of Patient-Derived Xenograft (PDX) Models of Human Breast Cancer.Curr Protoc Mouse Biol2013;3:21-9
|
| [22] |
Kanaya N,Wu J.Characterization of patient-derived tumor xenografts (PDXs) as models for estrogen receptor positive (ER+HER2- and ER+HER2+) breast cancers.J Steroid Biochem Mol Biol2017;170:65-74 PMCID:PMC5094906
|
| [23] |
Lefley D,Arshad F.Development of clinically relevant in vivo metastasis models using human bone discs and breast cancer patient-derived xenografts.Breast Cancer Res2019;21:130 PMCID:PMC6884811
|
| [24] |
Okada S,Kariya R.Application of Highly Immunocompromised Mice for the Establishment of Patient-Derived Xenograft (PDX) Models.Cells2019;8:889 PMCID:PMC6721637
|
| [25] |
Han Y,Hayashi Y.Establishment and characterization of highly osteolytic luminal breast cancer cell lines by intracaudal arterial injection.Genes Cells2020;25:111-23
|
| [26] |
Yi B,Niewolna M,Yoneda T.Tumor-derived platelet-derived growth factor-BB plays a critical role in osteosclerotic bone metastasis in an animal model of human breast cancer.Cancer Res2002;62:917-23.
|
| [27] |
Isoda T,Maruoka Y.Influence of the Different Primary Cancers and Different Types of Bone Metastasis on the Lesion-based Artificial Neural Network Value Calculated by a Computer-aided Diagnostic System, BONENAVI, on Bone Scintigraphy Images.Asia Ocean J Nucl Med Biol2017;5:49-55 PMCID:PMC5221686
|
| [28] |
Tamura D,Myoui A,Yoneda T.Cadherin-11-mediated interactions with bone marrow stromal/osteoblastic cells support selective colonization of breast cancer cells in bone.Int J Oncol2008;33:17-24.
|
| [29] |
Pécheur I,Serre CM.Integrin alpha(v)beta3 expression confers on tumor cells a greater propensity to metastasize to bone.FASEB J2002;16:1266-8
|
| [30] |
Kang Y,Shu W.A multigenic program mediating breast cancer metastasis to bone.Cancer Cell2003;3:537-49
|
| [31] |
Wetterwald A,Que I.Optical Imaging of Cancer Metastasis to Bone Marrow.Am J Pathol2002;160:1143-53 PMCID:PMC1867183
|
| [32] |
Bishop RT,Carrasco G.Combined administration of a small-molecule inhibitor of TRAF6 and Docetaxel reduces breast cancer skeletal metastasis and osteolysis.Cancer Lett2020;488:27-39
|
| [33] |
Bishop RT,de Ridder D.Pharmacological inhibition of the IKKε/TBK-1 axis potentiates the anti-tumour and anti-metastatic effects of Docetaxel in mouse models of breast cancer.Cancer Lett2019;450:76-87
|
| [34] |
Fathers KE,Rajadurai CV.Crk adaptor proteins act as key signaling integrators for breast tumorigenesis.Breast Cancer Res2012;14:R74 PMCID:PMC3446336
|
| [35] |
Werbeck JL,Martin CK.Tumor microenvironment regulates metastasis and metastasis genes of mouse MMTV-PymT mammary cancer cells in vivo.Vet Pathol2014;51:868-81 PMCID:PMC4291313
|
| [36] |
Ottewell PD,Lefley DV,Coleman RE.Anticancer mechanisms of doxorubicin and zoledronic acid in breast cancer tumor growth in bone.Mol Cancer Ther2009;8:2821-32
|
| [37] |
Zhou Y,Liu S.Monitoring Breast Tumor Lung Metastasis by U-SPECT-II/CT with an Integrin α(v)β(3)-Targeted Radiotracer( 99m)Tc-3P-RGD(2).Theranostics2012;2:577-88 PMCID:PMC3381346
|
| [38] |
Allocca G,Wang N.The bone metastasis niche in breast cancer-potential overlap with the haematopoietic stem cell niche in vivo.J Bone Oncol2019;17:100244 PMCID:PMC6582079
|
| [39] |
Peinado H,Matei IR.Pre-metastatic niches: organ-specific homes for metastases.Nat Rev Cancer2017;17:302-17
|
| [40] |
Holen I,Nutter F.Oestrogen receptor positive breast cancer metastasis to bone: inhibition by targeting the bone microenvironment in vivo.Clin Exp Metastasis2016;33:211-24
|
| [41] |
Wang N,Brown HK.The frequency of osteolytic bone metastasis is determined by conditions of the soil, not the number of seeds; evidence from in vivo models of breast and prostate cancer.J Exp Clin Cancer Res2015;34:124 PMCID:PMC4615337
|
| [42] |
Ottewell PD,Brown HK.Zoledronic acid has differential antitumor activity in the pre- and postmenopausal bone microenvironment in vivo.Clin Cancer Res2014;20:2922-32 PMCID:PMC4040234
|
| [43] |
Ottewell PD,Brown HK.OPG-Fc inhibits ovariectomy-induced growth of disseminated breast cancer cells in bone.Int J Cancer2015;137:968-77
|
| [44] |
Cailleau R,Olivé M.Breast tumor cell lines from pleural effusions.J Natl Cancer Inst1974;53:661-74 PMCID:PMC7364228
|
| [45] |
Sher E,Moseley JM.Whole-cell uptake and nuclear localization of 1,25-dihydroxycholecalciferol by breast cancer cells (T47 D) in culture.Biochem J1981;200:315-20 PMCID:PMC1163537
|
| [46] |
Lv X,Ding Y,Lewis MT.Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer.J Vis Exp2020;(159):10.3791/61173 PMCID:PMC7927877
|
| [47] |
Fatima I,Playa HC.Simultaneous Multi-Organ Metastases from Chemo-Resistant Triple-Negative Breast Cancer Are Prevented by Interfering with WNT-Signaling.Cancers (Basel)2019;11:2039 PMCID:PMC6966654
|
| [48] |
Giuliano M,Christiny P.Circulating and disseminated tumor cells from breast cancer patient-derived xenograft-bearing mice as a novel model to study metastasis.Breast Cancer Res2015;17:3 PMCID:PMC4318479
|
| [49] |
Pillai SG,Siddappa CM,Watson MA.Identifying biomarkers of breast cancer micrometastatic disease in bone marrow using a patient-derived xenograft mouse model.Breast Cancer Res2018;20:2 PMCID:PMC5748947
|
| [50] |
Zhang W,Wang H,Zhang XH.Bone Metastasis: Find Your Niche and Fit in.Trends Cancer2019;5:95-110 PMCID:PMC6383208
|
| [51] |
Kuperwasser C,Bierbaum BE.A mouse model of human breast cancer metastasis to human bone.Cancer Res2005;65:6130-8
|
| [52] |
Lam P,Amemiya Y.A human bone NOD/SCID mouse model to distinguish metastatic potential in primary breast cancers.Cancer Biol Ther2009;8:1010-7
|
| [53] |
Holen I,Wilkinson JM,Avgoustou P.Human breast cancer bone metastasis in vitro and in vivo: a novel 3D model system for studies of tumour cell-bone cell interactions.Clin Exp Metastasis2015;32:689-702.
|
| [54] |
Yang W,Kitching R.Breast cancer metastasis in a human bone NOD/SCID mouse model.Cancer Biol Ther2007;6:1289-94
|
| [55] |
Ottewell PD,Holen I.From genetic abnormality to metastases: murine models of breast cancer and their use in the development of anticancer therapies.Breast Cancer Res Treat2006;96:101-13
|
| [56] |
Derksen PW,van der Burg E.Mammary-specific inactivation of E-cadherin and p53 impairs functional gland development and leads to pleomorphic invasive lobular carcinoma in mice.Dis Model Mech2011;4:347-58 PMCID:PMC3097456
|
| [57] |
Céspedes MV,Parreño M.Mouse models in oncogenesis and cancer therapy.Clin Transl Oncol2006;8:318-29
|
| [58] |
Nandi S,Yang J.Hormones and mammary carcinogenesis in mice, rats, and humans: a unifying hypothesis.Proc Natl Acad Sci U S A1995;92:3650-7 PMCID:PMC42019
|
| [59] |
Buijs JT,Cheung H.Spontaneous bone metastases in a preclinical orthotopic model of invasive lobular carcinoma; the effect of pharmacological targeting TGFβ receptor I kinase.J Pathol2015;235:745-59 PMCID:PMC4407922
|
| [60] |
Pulaski BA.Mouse 4T1 breast tumor model.Curr Protoc Immunol2001;Chapter 20:Unit 20.2
|
| [61] |
Tulotta CM,Amariutei AE.Inhibition of breast cancer bone metastasis through Interleukin-1B regulated tumour-associated innate immune response.Breast Cancer Res Treat2020;180:538-9
|
| [62] |
Hiraga T.Establishment and characterization of a C57BL/6 mouse model of bone metastasis of breast cancer.J Bone Miner Metab2019;37:235-42
|
| [63] |
Zhou JZ,Gao X,Sun LZ.Differential impact of adenosine nucleotides released by osteocytes on breast cancer growth and bone metastasis.Oncogene2015;34:1831-42 PMCID:PMC4315766
|
| [64] |
Cox TC.Microcomputed tomography of craniofacial mineralized tissue: A practical user's guide to study planning and generating quality data.Bone2020;137:115408
|
| [65] |
Green AC,Hudson K.TGFβ Inhibition Stimulates Collagen Maturation to Enhance Bone Repair and Fracture Resistance in a Murine Myeloma Model.J Bone Miner Res2019;34:2311-26
|
| [66] |
Paton-Hough J,Evans H.Preventing and Repairing Myeloma Bone Disease by Combining Conventional Antiresorptive Treatment With a Bone Anabolic Agent in Murine Models.J Bone Miner Res2019;34:783-96 PMCID:PMC6607020
|
| [67] |
Westbrook JA,Peng J.CAPG and GIPC1: Breast Cancer Biomarkers for Bone Metastasis Development and Treatment.J Natl Cancer Inst2016;108 PMCID:PMC4808632
|
| [68] |
Monteran L,Sabah I.Bone metastasis is associated with acquisition of mesenchymal phenotype and immune suppression in a model of spontaneous breast cancer metastasis.Sci Rep2020;10:13838 PMCID:PMC7429866
|
| [69] |
Yao L,Cheng M,Keck JG.Creation of PDX-Bearing Humanized Mice to Study Immuno-oncology. In: Moll J, Carotta S, editors. Target Identification and Validation in Drug Discovery. New York: Springer; 2019. pp. 241-52.
|
| [70] |
Hasgur S,Shultz LD,Brehm MA.Generation of Immunodeficient Mice Bearing Human Immune Systems by the Engraftment of Hematopoietic Stem Cells. In: Proetzel G, Wiles MV, editors. Mouse Models for Drug Discovery. New York: Springer; 2016. pp. 67-78. PMCID:PMC5268072
|
| [71] |
Wege AK,Eckl J.Humanized tumor mice-a new model to study and manipulate the immune response in advanced cancer therapy.Int J Cancer2011;129:2194-206
|