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Review old bone, new tricks

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Abstract

Despite the significant progress made over the past decade with combination of molecular profiling data and the development of new clinical strategies, our understanding of metastasis remains elusive. Bone metastasis is a complex process and a major cause of mortality in breast and prostate cancer patients, for which there is no effective treatment to-date. The current review summarizes the routes taken by the metastatic cells and the interactions between them and the bone microenvironment. We emphasize the role of the specified niches and cues that promote cellular adhesion, colonization, prolonged dormancy, and reactivation. Understanding these mechanisms will provide better insights for future studies and treatment strategies for bone metastatic conditions.

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References

  1. Schmid-Alliana A, Schmid-Antomarchi H, Al-Sahlanee R, Lagadec P, Scimeca J, Verron E Understanding the Progression of Bone Metastases to Identify Novel Therapeutic Targets.International journal of molecular sciences. 2018 Jan4,;19(1):148

  2. Macedo F, Ladeira K, Pinho F, Saraiva N, Bonito N, Pinto L et al (2017) Bone metastases: an overview. Oncol reviews 11(1):321

    Google Scholar 

  3. Zhang W, Bado I, Wang H, Lo H, Zhang XH- (2019 Feb) Bone Metastasis: Find Your Niche and Fit in. Trends in Cancer 5(2):95–110

  4. Kalluri R, Weinberg RA (2009 Jun) The basics of epithelial-mesenchymal transition. J Clin Invest 119(6):1420–1428

  5. Marusyk A, Polyak K (2010) Tumor heterogeneity: Causes and consequences. Biochimica et biophysica acta. Reviews on cancer 1805(1):105–117

    CAS  Google Scholar 

  6. Tracey A, Martin L, Ye AJ, Sanders J, Lane, Wen G (2013) Jiang. Cancer Invasion and Metastasis: Molecular and Cellular Perspective. Madame Curie Bioscience Database

  7. Ottewell PD, O’Donnell L, Holen I (2015) Molecular alterations that drive breast cancer metastasis to bone. BoneKEy Rep 4:643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Wood S, Salawu A, Kroening H, D’Oronzo S, Brown J (2019) Bone metastases; Clinical aspects.Elsevier.

  9. Florencio-Silva R, Sasso E, Simões MJ, Cerri PS (2015) Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells. BioMed research international. ;2015:1–17

  10. Wang H, Zhang W, Bado I, Zhang XH- Bone Tropism in Cancer Metastases. Cold Spring Harbor perspectives in medicine.2019 Oct15,:a036848

  11. Wang H, Pan J, Barsky L, Jacob JC, Zheng Y, Gao C et al Characteristics of pre-metastatic niche: the landscape of molecular and cellular pathways.Mol Biomed. 2021 Jan30,;2(1):3

  12. Bonnans C, Chou J, Werb Z (2014) Remodelling the extracellular matrix in development and disease. Nat Rev Mol Cell Biol 15(12):786–801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Gattazzo F, Urciuolo A, Bonaldo P (2014) Extracellular matrix: A dynamic microenvironment for stem cell niche. Biochimica et biophysica acta. Gen Subj 1840(8):2506–2519

    Article  CAS  Google Scholar 

  14. Novoseletskaya ES, Grigorieva OA, Efimenko AY, Kalinina NI (2019) Extracellular Matrix in the Regulation of Stem Cell Differentiation. Biochem Mosc 84(3):232–240

    Article  CAS  Google Scholar 

  15. Lin X, Patil S, Gao Y, Qian A The Bone Extracellular Matrix in Bone Formation and Regeneration. Frontiers in pharmacology.2020 May26,;11:757

  16. Feng X, McDonald JM (2011) Disorders of Bone Remodeling. Annu Rev Pathol 6(1):121–145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini FC, Krause DS et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8(4):315–317

    Article  CAS  PubMed  Google Scholar 

  18. Morrison SJ, Scadden DT (2014) The bone marrow niche for haematopoietic stem cells. Nat (London) 505(7483):327–334

    Article  CAS  Google Scholar 

  19. Anthony BA, Link DC (2014) Regulation of hematopoietic stem cells by bone marrow stromal cells. Trends Immunol 35(1):32–37

    Article  CAS  PubMed  Google Scholar 

  20. Caplan AI, All (2008) MSCs Are Pericytes? Cell stem cell 3(3):229–230

    Article  CAS  PubMed  Google Scholar 

  21. Haider M, Smit DJ, Taipaleenmäki H (2020) The Endosteal Niche in Breast Cancer Bone Metastasis. Front Oncol 10:335

    Article  PubMed  PubMed Central  Google Scholar 

  22. Carvalho MS, Cabral JM, da Silva CL, Vashishth D (2019) Synergistic effect of extracellularly supplemented osteopontin and osteocalcin on stem cell proliferation, osteogenic differentiation, and angiogenic properties. J Cell Biochem 120(4):6555–6569

    Article  CAS  PubMed  Google Scholar 

  23. Knight MN, Karuppaiah K, Lowe M, Mohanty S, Zondervan RL, Bell S et al (2018) R-spondin-2 is a Wnt agonist that regulates osteoblast activity and bone mass. Bone Res 6(1):24–14

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Crane GM, Jeffery E, Morrison SJ (2017) Adult haematopoietic stem cell niches. Nat Rev Immunol 17(9):573–590

    Article  CAS  PubMed  Google Scholar 

  25. Kumar S, Geiger H (2017) HSC Niche Biology and HSC Expansion Ex Vivo. Trends Mol Med 23(9):799–819

    Article  PubMed  PubMed Central  Google Scholar 

  26. Byrne NM, Summers MA, McDonald MM (2019) Tumor Cell Dormancy and Reactivation in Bone: Skeletal Biology and Therapeutic Opportunities. JBMR plus. Mar;3(3):e10125

  27. Nusse R, Fuerer C, Ching W, Harnish K, Logan C, Zeng A et al (2008) Wnt Signaling and Stem Cell Control. Cold Spring Harb Symp Quant Biol 73:59–66

    Article  CAS  PubMed  Google Scholar 

  28. Kai F, Drain AP, Weaver VM (2019) The Extracellular Matrix Modulates the Metastatic Journey. Dev Cell 49(3):332–346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Celià-Terrassa T, Kang Y (2016) Distinctive properties of metastasis-initiating cells. Genes Dev 30(8):892–908

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Baccelli I, Trumpp A (2012) The evolving concept of cancer and metastasis stem cells. J Cell Biol 198(3):281–293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Oskarsson T, Batlle E, Massagué J (2014) Metastatic Stem Cells: Sources, Niches, and Vital Pathways. Cell Stem Cell 14(3):306–321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Baccelli I, Schneeweiss A, Riethdorf S, Stenzinger A, Schillert A, Vogel V et al (2013) Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay. Nat Biotechnol 31(6):539–544

    Article  CAS  PubMed  Google Scholar 

  33. Hung K, Yang T, Kao S (2019) Cancer stem cell theory. J Chin Med Association –11(11):814

    Article  Google Scholar 

  34. Tu S, Zhang M, Wood CG, Pisters LL Stem Cell Theory of Cancer: Origin of Tumor Heterogeneity and Plasticity.Cancers. 2021 Aug09,;13(16):4006

  35. Tu S, Guo CC, Chow DS, Zacharias NM Stem Cell Theory of Cancer: Implications for Drug Resistance and Chemosensitivity in Cancer Care.Cancers. 2022 Mar18,;14(6):1548

  36. Lawson MA, McDonald MM, Kovacic N, Hua Khoo W, Terry RL, Down J et al (2015) Osteoclasts control reactivation of dormant myeloma cells by remodelling the endosteal niche. Nat Commun 6(1):8983

    Article  CAS  PubMed  Google Scholar 

  37. Allocca G, Hughes R, Wang N, Brown HK, Ottewell PD, Brown NJ et al (2019) The bone metastasis niche in breast cancer: potential overlap with the haematopoietic stem cell niche in vivo. J bone Oncol 17:100244

    Article  PubMed  PubMed Central  Google Scholar 

  38. Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C et al (2005) VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nat (London) 438(7069):820–827

    Article  CAS  Google Scholar 

  39. Liu Y, Cao X (2016) Characteristics and Significance of the Pre-metastatic Niche. Cancer Cell 30(5):668–681

    Article  CAS  PubMed  Google Scholar 

  40. Erler JT, Bennewith KL, Cox TR, Lang G, Bird D, Koong A et al Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the pre-metastatic niche.Cancer Cell. 2009 Jan6,;15(1):35–44

  41. Ursini-Siegel J, Siegel PM (2016) The influence of the pre-metastatic niche on breast cancer metastasis. Cancer Lett 380(1):281–288

    Article  CAS  PubMed  Google Scholar 

  42. Celià-Terrassa T, Kang Y (2018) Metastatic niche functions and therapeutic opportunities. Nat Cell Biol 20(8):868–877

    Article  PubMed  CAS  Google Scholar 

  43. Cox RF, Jenkinson A, Pohl K, O’Brien FJ, Morgan MP. Osteomimicry of Mammary Adenocarcinoma Cells In Vitro; Increased Expression of Bone Matrix Proteins and Proliferation within a 3D Collagen Environment. PLoS ONE. 2012;7(7):e41679

  44. Ishay-Ronen D, Diepenbruck M, Kalathur RKR, Sugiyama N, Tiede S, Ivanek R et al Gain Fat—Lose Metastasis: Converting Invasive Breast Cancer Cells into Adipocytes Inhibits Cancer Metastasis.Cancer cell. 2019 Jan14,;35(1):17,32.e6

  45. Weilbaecher KN, Guise TA, McCauley LK (2011) Cancer to bone: a fatal attraction. Nat Rev Cancer 11(6):411–425

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. D’Oronzo S, Coleman R, Brown J, Silvestris F (2019 Apr) Metastatic bone disease: Pathogenesis and therapeutic options: Up-date on bone metastasis management. J bone Oncol 15:004

  47. Esposito M, Mondal N, Greco TM, Wei Y, Spadazzi C, Lin S et al (2019) Bone vascular niche E-selectin induces mesenchymal–epithelial transition and Wnt activation in cancer cells to promote bone metastasis. Nat Cell Biol 21(5):627–639

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Song K, Farzaneh M. Signaling pathways governing breast cancer stem cells behavior. Stem cell research and therapy. 2021 Apr 16, 12(1):245

  49. Marei WF, Ghafari F, Fouladi-Nashta AA (2012 Aug) Role of hyaluronic acid in maturation and further early embryo development of bovine oocytes. Theriogenology 78(3):670–677

  50. Ouhtit A, Rizeq B, Saleh HA, Rahman MM, Zayed H (2018) Novel CD44-downstream signaling pathways mediating breast tumor invasion. Int J Biol Sci 14(13):1782–1790

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Brown RL, Reinke LM, Damerow MS, Perez D, Chodosh LA, Yang J et al (2011 Mar) CD44 splice isoform switching in human and mouse epithelium is essential for epithelial-mesenchymal transition and breast cancer progression. J Clin Invest 121(3):1064–1074

  52. Ponzetti M, Rucci N Switching Homes: How Cancer Moves to Bone.International journal of molecular sciences. 2020 Jun9,;21(11):4124

  53. Zheng H, Bae Y, Kasimir-Bauer S, Tang R, Chen J, Ren G et al Therapeutic Antibody Targeting Tumor- and Osteoblastic Niche-Derived Jagged1 Sensitizes Bone Metastasis to Chemotherapy.Cancer cell. 2017 Dec11,;32(6):731,747.e6

  54. Bado IL, Zhang W, Hu J, Xu Z, Wang H, Sarkar P et al The bone microenvironment increases phenotypic plasticity of ER + breast cancer cells.Developmental cell. 2021 Apr19,;56(8):1100,1117.e9

  55. Zhang W, Bado IL, Hu J, Wan Y, Wu L, Wang H et al The bone microenvironment invigorates metastatic seeds for further dissemination.Cell. 2021 Apr29,;184(9):2471,2486.e20

  56. Gawrzak S, Rinaldi L, Gregorio S, Arenas EJ, Salvador F, Urosevic J et al MSK1 regulates luminal cell differentiation and metastatic dormancy in ER + breast cancer.Nat Cell Biol.; 20(2):211

  57. Massagué J, Tavazoie SF, Alarcón C, Oskarsson T, Padua D, Wang Q et al Endogenous human microRNAs that suppress breast cancer metastasis.Nature (London). 2008 Jan10,;451(7175):147–52

  58. Tiwari N, Tiwari V, Waldmeier L, Balwierz P, Arnold P, Pachkov M et al Sox4 Is a Master Regulator of Epithelial-Mesenchymal Transition by Controlling Ezh2 Expression and Epigenetic Reprogramming.Cancer cell. 2013 Jun10,;23(6):768–83

  59. Zhang P, Xiao Z, Wang S, Zhang M, Wei Y, Hang Q et al ZRANB1 Is an EZH2 Deubiquitinase and a Potential Therapeutic Target in Breast Cancer.Cell Reports. 2018 Apr17,;23(3):823–37

  60. Sethi N, Dai X, Winter CG, Kang Y (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  PubMed  PubMed Central  Google Scholar 

  61. Peinado H, Alečković M, Lavotshkin S, Matei I, Costa-Silva B, Moreno-Bueno G et al (2012 Jun) Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med 18(6):883–891

  62. Mathieu M, Martin-Jaular L, Lavieu G, Théry C (2019) Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat Cell Biol –01(1):9

    Article  CAS  Google Scholar 

  63. Hoshino A, Costa-Silva B, Shen T, Rodrigues G, Hashimoto A, Tesic Mark M et al Tumour exosome integrins determine organotropic metastasis.Nature. 2015-10-28;527(7578):329

  64. Cox TR, Rumney RMH, Schoof EM, Perryman L, Hoye AM, Agrawal A et al The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase.Nature. 2015 Jun4,;522(7544):106

  65. Gomis RR, Gawrzak S (2017) Tumor cell dormancy. Mol Oncol 11(1):62–78

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Park S, Nam J (2020 Apr) The force awakens: metastatic dormant cancer cells. Exp Mol Med 52(4):569–581

  67. Mayhew V, Omokehinde T, Johnson RW (2019) Tumor dormancy in bone. Cancer Rep 3(1):e1156. ,n/a

    Google Scholar 

  68. Endo H, Inoue M (2019) Dormancy in cancer. Cancer Sci 110(2):474–480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Sosa MS, Avivar-Valderas A, Bragado P, Wen H, Aguirre-Ghiso JA (2011) ERK1/2 and p38α/β Signaling in Tumor Cell Quiescence: Opportunities to Control Dormant Residual Disease. Clin Cancer Res 17(18):5850–5857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Aguirre-Ghiso JA, Estrada Y, Ossowski L ERKMAPK Activity as a Determinant of Tumor Growth and Dormancy; Regulation by p38SAPK.Cancer Research. 2003 Apr,;63(7).

  71. Mebratu Y, Tesfaigzi Y (2014) How ERK1/2 activation controls cell proliferation and cell death: Is subcellular localization the answer? Cell Cycle 8(8):1168–1175

    Article  Google Scholar 

  72. Shupp AB, Kolb AD, Mukhopadhyay D, Bussard KM (2018) Cancer Metastases to Bone: Concepts, Mechanisms, and Interactions with Bone Osteoblasts. Cancers 10(6):182

    Article  PubMed Central  CAS  Google Scholar 

  73. Yu-Lee L, Lee Y, Pan J, Lin S, Pan T, Yu G et al (2019) Bone secreted factors induce cellular quiescence in prostate cancer cells. Sci Rep 9(1):18635–18619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Sowder ME, Johnson RW (2019) Bone as a Preferential Site for Metastasis. JBMR plus 3(3):e10126

    Article  PubMed  PubMed Central  Google Scholar 

  75. Zhan T, Rindtorff N, Boutros M (2016) Wnt signaling in cancer. Oncogene 36(11):1461–1473

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Ren D, Dai Y, Yang Q, Zhang X, Guo W, Ye L et al (2019) Wnt5a induces and maintains prostate cancer cells dormancy in bone. J Exp Med 216(2):428–449

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Ghajar CM, Peinado H, Mori H, Matei IR, Evason KJ, Brazier H et al (2013) The perivascular niche regulates breast tumour dormancy. Nat Cell Biol 15(7):807–817

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Shemanko C, Cong Y, Forsyth A (2016) What Is Breast in the Bone? Int J Mol Sci 17(10):1764

    Article  PubMed Central  CAS  Google Scholar 

  79. Oh M, Nör JE (2015) The Perivascular Niche and Self-Renewal of Stem Cells. Front Physiol 6:367

    Article  PubMed  PubMed Central  Google Scholar 

  80. Lecarpentier Y, Schussler O, Hébert J, Vallée A (2019) Multiple Targets of the Canonical WNT/β-Catenin Signaling in Cancers. Front Oncol 9:1248

    Article  PubMed  PubMed Central  Google Scholar 

  81. Kingsley LA, Fournier PGJ, Chirgwin JM, Guise TA (2007) Molecular Biology of Bone Metastasis. Mol Cancer Ther 6(10):2609–2617

    Article  CAS  PubMed  Google Scholar 

  82. Guise TA, Yin JJ, Taylor SD, Kumagai Y, Dallas M, Boyce BF et al Evidence for a causal role of parathyroid hormone-related protein in the pathogenesis of human breast cancer-mediated osteolysis.The Journal of clinical investigation. 1996 Oct1,;98(7):1544–9

  83. Johnson RW, Sun Y, Ho PWM, Chan ASM, Johnson JA, Pavlos NJ et al (2018) Parathyroid Hormone-Related Protein Negatively Regulates Tumor Cell Dormancy Genes in a PTHR1/Cyclic AMP-Independent Manner. 9:241 Frontiers in endocrinology (Lausanne)

  84. Käkönen S, Selander KS, Chirgwin JM, Yin JJ, Burns S, Rankin WA et al (2002) Transforming Growth Factor-β Stimulates Parathyroid Hormone-related Protein and Osteolytic Metastases via Smad and Mitogen-activated Protein Kinase Signaling Pathways. J Biol Chem 277(27):24571–24578

    Article  PubMed  CAS  Google Scholar 

  85. Xu X, Zheng L, Yuan Q, Zhen G, Crane JL, Zhou X et al (2018) Transforming growth factor-β in stem cells and tissue homeostasis. Bone Res 6(1):2–31

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Henderson MA, Danks JA, Slavin JL, Byrnes GB, Choong PF, Spillane JB et al Parathyroid Hormone-Related Protein Localization in Breast Cancers Predict Improved Prognosis.Cancer Research. 2006 Feb1,;66(4):2250–6

  87. Xu C, Wang Z, Cui R, He H, Lin X, Sheng Y et al Co-expression of parathyroid hormone related protein and TGF-beta in breast cancer predicts poor survival outcome.BMC cancer. 2015 Nov23,;15(923):925

  88. Jinnah AH, Zacks BC, Gwam CU, Kerr BA Emerging and Established Models of Bone Metastasis.Cancers. 2018 Jun1,;10(6):176

  89. Bendre MS, Margulies AG, Walser B, Akel NS, Bhattacharrya S, Skinner RA et al (2005) Tumor-Derived Interleukin-8 Stimulates Osteolysis Independent of the Receptor Activator of Nuclear Factor-κB Ligand Pathway. Cancer Res (Chicago Ill) 65(23):11001–11009

    Article  CAS  Google Scholar 

  90. Guise TA (2002 Dec) The vicious cycle of bone metastases. J Musculoskel Neuronal Interact 2(6):570

  91. Nakai M, Mundy GR, Williams PJ, Boyce B, Yoneda T A synthetic antagonist to laminin inhibits the formation of osteolytic metastases by human melanoma cells in nude mice.Cancer Res. 1992-10-01; 52(19):5395–9

  92. Li X, Sterling JA, Fan K, Vessella RL, Shyr Y, Hayward SW et al (2012 Apr) Loss of TGF-β responsiveness in prostate stromal cells alters chemokine levels and facilitates the development of mixed osteoblastic/osteolytic bone lesions. Mol cancer Res 10(4):494–503

  93. Yu C, Wang H, Muscarella A, Goldstein A, Zeng H, Bae Y et al (2016) Intra-iliac Artery Injection for Efficient and Selective Modeling of Microscopic Bone Metastasis.JoVE. -09(115).

  94. Kuchimaru T, Kataoka N, Nakagawa K, Isozaki T, Miyabara H, Minegishi M et al A reliable murine model of bone metastasis by injecting cancer cells through caudal arteries.Nature Communications. 2018 Jul30,;9(1):2981–7

  95. Thibaudeau L, Taubenberger AV, Holzapfel BM, Quent VM, Fuehrmann T, Hesami P, et al. A tissue-engineered humanized xenograft model of human breast cancer metastasis to bone. Disease models & mechanisms. 2014 Feb;7(2):299-309

  96. Kuperwasser C, Dessain S, Bierbaum BE, Garnet D, Sperandio K, Gauvin GP et al A Mouse Model of Human Breast Cancer Metastasis to Human Bone.Cancer Research. 2005 Jul15,;65(14):6130–8

  97. Wang H, Tian L, Goldstein A, Liu J, Lo H, Sheng K et al Bone-in-culture array as a platform to model early-stage bone metastases and discover anti-metastasis therapies.Nat Commun. 2017-04-21;8(1).

  98. Levinger I, Zagouri R, Ventura Y, Vago R Effects of Three Dimensional Microenvironment on Tumorigenicity of Fibrosarcoma in vitro. Cancer Studies and Molecular Medicine -Open Journal. 2014 Dec15,;1(1):16–26

  99. Montagner M, Sahai E (2020) In vitro Models of Breast Cancer Metastatic Dormancy. Front cell Dev biology 8:37

    Article  Google Scholar 

  100. Piccolo S, Dupont S, Cordenonsi M (2014 Oct) The biology of yap/taz: Hippo signaling and beyond. Physiological reviews 94(4):1287–1312

  101. Iskratsch T, Wolfenson H, Sheetz MP (2014 Dec) Appreciating force and shape — the rise of mechanotransduction in cell biology. Nat reviews Mol cell biology 15(12):825–833

  102. Montagner M, Dupont S Mechanical Forces as Determinants of Disseminated Metastatic Cell Fate.Cells. 2020 Jan19,;9(1):250

  103. Astachov L, Nevo Z, Vago R (2012) Calcite Biohybrids as Microenvironment for Stem Cells. Polymers 4(2):1065–1083

    Article  CAS  Google Scholar 

  104. Zhu W, Wang M, Fu Y, Castro NJ, Fu SW, Zhang LG (2015) Engineering a biomimetic three-dimensional nanostructured bone model for breast cancer bone metastasis study. Acta Biomater 14:164–174

    Article  CAS  PubMed  Google Scholar 

  105. Li W, Hu X, Wang S, Xing Y, Wang H, Nie Y et alMultiple comparisons of three different sources of biomaterials in the application of tumor (2019) tissue engineering in vitro and in vivo. Int J Biol Macromol 130:166–176

  106. James-Bhasin M, Siegel P, Nazhat S (2018) A Three-Dimensional Dense Collagen Hydrogel to Model Cancer Cell/Osteoblast Interactions. J Funct biomaterials 9(4):72

    Article  CAS  Google Scholar 

  107. Birk RZ, Abramovitch-Gottlib L, Margalit I, Aviv M, Forti E, Geresh S et al (2006 Jan) Conversion of Adipogenic to Osteogenic Phenotype Using Crystalline Porous Biomatrices of Marine Origin. Tissue Eng 12(1):21–31

  108. Abramovitch-Gottlib L, Geresh S, Vago R (2006 Apr) Biofabricated Marine Hydrozoan: A Bioactive Crystalline Material Promoting Ossification of Mesenchymal Stem Cells. Tissue Eng 12(4):729–739

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Acknowledgements

The work was supported in part, by Kamin Incentive Program, The Israel Innovative Authority. The figures were created using adapted images from Servier Medical Art by Servier, licensed under a Creative Commons Attribution 3.0 Unported License.

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  1. Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev, 84105, Beer-Sheva, Israel

    Livnat Barsky, Ifat Cohen-Erez & Razi Vago

  2. Lester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, 77030, Houston, TX, USA

    Igor Bado & Xiang H-F Zhang

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  1. Livnat Barsky
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Barsky, L., Cohen-Erez, I., Bado, I. et al. Review old bone, new tricks. Clin Exp Metastasis 39, 727–742 (2022). https://doi.org/10.1007/s10585-022-10176-5

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