Skip to main content

Oncodynamic Changes in Skeleton

  • Chapter
  • First Online:
Oncodynamics: Effects of Cancer Cells on the Body
  • 449 Accesses

Abstract

When cancers are present in bone, a number of complex changes occur that can alter the physiology and structure of the skeleton. To properly understand these oncodynamic processes—how the bone changes in response to cancer cell invasion—it is necessary to define the types of cells that are present in normal bone, to explore the main physiological functions of these cells and of the bone itself, and to describe the types of cancers that often grow in bone. To properly characterize the functional and anatomical responses of bone cells, a broader definition of what cell types are present in bone is required. Using a more comprehensive and inclusive definition of bone cells, adaptations that result from cancer cell invasion can be categorized on the basis of the signalled functional and structural changes that occur between all involved cells in the bone environment. These pathological responses will be integrated with what is known about the chemical mediators that may be involved. This analysis of the normal signalling environment in bone and the potential interactions between cell types will help to better characterize the complex oncodynamic processes that can occur when cancer invades bone and disrupts this carefully balanced microenvironment.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Van PC, Somerfield MR, Bast RC, Cristofanilli M, Goetz MP, Gonzalez-Angulo AM, et al. Use of biomarkers to guide decisions on systemic therapy for women with metastatic breast cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2015;33(24):2695–704.

    Article  Google Scholar 

  2. Wagner DO, Aspenberg P. Where did bone come from? Acta Orthop. 2011;82(4):393–8.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Donoghue PC, Sansom IJ. Origin and early evolution of vertebrate skeletonization. Microsc Res Tech. 2002;59(5):352–72.

    Article  PubMed  Google Scholar 

  4. Sahni A. Biomineralization: some complex crystallite-oriented skeletal structures. J Biosci. 2013;38(5):925–35.

    Article  PubMed  CAS  Google Scholar 

  5. Ruben JA, Bennett AA. The evolution of bone. Evolution. 1987;41(6):1187–97.

    Article  Google Scholar 

  6. Donoghue PC, Sansom IJ, Downs JP. Early evolution of vertebrate skeletal tissues and cellular interactions, and the canalization of skeletal development. J Exp Zool B Mol Dev Evol. 2006;306(3):278–94.

    Article  PubMed  CAS  Google Scholar 

  7. Herberger AL, Loretz CA. Vertebrate extracellular calcium-sensing receptor evolution: selection in relation to life history and habitat. Comp Biochem Physiol Part D Genomics Proteomics. 2013;8(1):86–94.

    Article  PubMed  CAS  Google Scholar 

  8. Taichman RS. Blood and bone: two tissues whose fates are intertwined to create the hematopoietic stem-cell niche. Blood. 2005;105(7):2631–9.

    Article  PubMed  CAS  Google Scholar 

  9. Oldknow KJ, MacRae VE, Farquharson C. Endocrine role of bone: recent and emerging perspectives beyond osteocalcin. J Endocrinol. 2015;225(1):R1–19.

    Article  PubMed  CAS  Google Scholar 

  10. Dallas SL, Prideaux M, Bonewald LF. The osteocyte: an endocrine cell … and more. Endocr Rev. 2013;34(5):658–90.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  11. Hu MC, Shiizaki K, Kuro-o M, Moe OW. Fibroblast growth factor 23 and Klotho: physiology and pathophysiology of an endocrine network of mineral metabolism. Annu Rev Physiol. 2013;75:503–33.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  12. Schwetz V, Pieber T, Obermayer-Pietsch B. The endocrine role of the skeleton: background and clinical evidence. Eur J Endocrinol. 2012;166(6):959–67.

    Article  PubMed  CAS  Google Scholar 

  13. Zhang Q, Riddle RC, Clemens TL. Bone and the regulation of global energy balance. J Intern Med. 2015;277(6):681–9.

    Article  PubMed  CAS  Google Scholar 

  14. Karsenty G, Oury F. Regulation of male fertility by the bone-derived hormone osteocalcin. Mol Cell Endocrinol. 2014;382(1):521–6.

    Article  PubMed  CAS  Google Scholar 

  15. Oury F, Sumara G, Sumara O, Ferron M, Chang H, Smith CE, et al. Endocrine regulation of male fertility by the skeleton. Cell. 2011;144(5):796–809.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  16. Oury F, Ferron M, Huizhen W, Confavreux C, Xu L, Lacombe J, et al. Osteocalcin regulates murine and human fertility through a pancreas-bone-testis axis. J Clin Invest. 2013;123(6):2421–33.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  17. D’Amelio P, Panico A, Spertino E, Isaia GC. Energy metabolism and the skeleton: reciprocal interplay. World J Orthop. 2012;3(11):190–8.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Andersen TL, Sondergaard TE, Skorzynska KE, Dagnaes-Hansen F, Plesner TL, Hauge EM, et al. A physical mechanism for coupling bone resorption and formation in adult human bone. Am J Pathol. 2009;174(1):239–47.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  19. Kular J, Tickner J, Chim SM, Xu J. An overview of the regulation of bone remodelling at the cellular level. Clin Biochem. 2012;45(12):863–73.

    Article  PubMed  CAS  Google Scholar 

  20. Hinoi E, Takarada T, Yoneda Y. Glutamate signaling system in bone. J Pharmacol Sci. 2004;94(3):215–20.

    Article  PubMed  CAS  Google Scholar 

  21. Palumbo C, Ferretti M, Ardizzoni A, Zaffe D, Marotti G. Osteocyte-osteoclast morphological relationships and the putative role of osteocytes in bone remodeling. J Musculoskelet Neuronal Interact. 2001;1(4):327–32.

    PubMed  CAS  Google Scholar 

  22. Skerry TM. The role of glutamate in the regulation of bone mass and architecture. J Musculoskelet Neuronal Interact. 2008;8(2):166–73.

    PubMed  CAS  Google Scholar 

  23. Stains JP, Civitelli R. Cell-to-cell interactions in bone. Biochem Biophys Res Commun. 2005;328(3):721–7.

    Article  PubMed  CAS  Google Scholar 

  24. Florencio-Silva R, Sasso GR, Sasso-Cerri E, Simoes MJ, Cerri PS. Biology of bone tissue: structure, function, and factors that influence bone cells. Biomed Res Int. 2015;2015:421746.

    Article  PubMed Central  PubMed  Google Scholar 

  25. Horowitz MC, Lorenzo JA. The origins of osteoclasts. Curr Opin Rheumatol. 2004;16(4):464–8.

    Article  PubMed  Google Scholar 

  26. Baron R. Polarity and membrane transport in osteoclasts. Connect Tissue Res. 1989;20(1–4):109–20.

    Article  PubMed  CAS  Google Scholar 

  27. Morimoto R, Uehara S, Yatsushiro S, Juge N, Hua Z, Senoh S, et al. Secretion of L-glutamate from osteoclasts through transcytosis. EMBO J. 2006;25(18):4175–86.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  28. Blair HC, Athanasou NA. Recent advances in osteoclast biology and pathological bone resorption. Histol Histopathol. 2004;19(1):189–99.

    PubMed  CAS  Google Scholar 

  29. Teitelbaum SL. Bone resorption by osteoclasts. Science. 2000;289(5484):1504–8.

    Article  PubMed  CAS  Google Scholar 

  30. Kylmaoja E, Nakamura M, Tuukkanen J. Osteoclasts and remodeling based bone formation. Curr Stem Cell Res Ther. 2015;19.

    Google Scholar 

  31. Cappariello A, Maurizi A, Veeriah V, Teti A. The great beauty of the osteoclast. Arch Biochem Biophys. 2014;15(558):70–8.

    Article  CAS  Google Scholar 

  32. Charles JF, Aliprantis AO. Osteoclasts: more than ‘bone eaters’. Trends Mol Med. 2014;20(8):449–59.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  33. Malaval L, Liu F, Roche P, Aubin JE. Kinetics of osteoprogenitor proliferation and osteoblast differentiation in vitro. J Cell Biochem. 1999;74(4):616–27.

    Article  PubMed  CAS  Google Scholar 

  34. Capulli M, Paone R, Rucci N. Osteoblast and osteocyte: games without frontiers. Arch Biochem Biophys. 2014;1(561):3–12.

    Article  CAS  Google Scholar 

  35. Aubin JE. Regulation of osteoblast formation and function. Rev Endocr Metab Disord. 2001;2(1):81–94.

    Article  PubMed  CAS  Google Scholar 

  36. Schaffler MB, Kennedy OD. Osteocyte signaling in bone. Curr Osteoporos Rep. 2012;10(2):118–25.

    Article  PubMed Central  PubMed  Google Scholar 

  37. Rosenberg N, Rosenberg O, Soudry M. Osteoblasts in bone physiology-mini review. Rambam Maimonides Med J. 2012;3(2):e0013.

    Article  PubMed Central  PubMed  Google Scholar 

  38. Krishnan V, Dhurjati R, Vogler EA, Mastro AM. Osteogenesis in vitro: from pre-osteoblasts to osteocytes: a contribution from the Osteobiology Research Group, The Pennsylvania State University. Vitro Cell Dev Biol Anim. 2010;46(1):28–35.

    Article  Google Scholar 

  39. Kamioka H, Sugawara Y, Honjo T, Yamashiro T, Takano-Yamamoto T. Terminal differentiation of osteoblasts to osteocytes is accompanied by dramatic changes in the distribution of actin-binding proteins. J Bone Miner Res. 2004;19(3):471–8.

    Article  PubMed  CAS  Google Scholar 

  40. Bellido T. Osteocyte-driven bone remodeling. Calcif Tissue Int. 2014;94(1):25–34.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  41. Neve A, Corrado A, Cantatore FP. Osteocytes: central conductors of bone biology in normal and pathological conditions. Acta Physiol (Oxf). 2012;204(3):317–30.

    Article  CAS  Google Scholar 

  42. Bonewald LF. The amazing osteocyte. J Bone Miner Res. 2011;26(2):229–38.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  43. Tomkinson A, Reeve J, Shaw RW, Noble BS. The death of osteocytes via apoptosis accompanies estrogen withdrawal in human bone. J Clin Endocrinol Metab. 1997;82(9):3128–35.

    PubMed  CAS  Google Scholar 

  44. Tanaka-Kamioka K, Kamioka H, Ris H, Lim SS. Osteocyte shape is dependent on actin filaments and osteocyte processes are unique actin-rich projections. J Bone Miner Res. 1998;13(10):1555–68.

    Article  PubMed  CAS  Google Scholar 

  45. Buenzli PR, Sims NA. Quantifying the osteocyte network in the human skeleton. Bone. 2015;75:144–50.

    Article  PubMed  CAS  Google Scholar 

  46. Winkler DG, Sutherland MK, Geoghegan JC, Yu C, Hayes T, Skonier JE, et al. Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO J. 2003;22(23):6267–76.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  47. Igwe JC, Jiang X, Paic F, Ma L, Adams DJ, Baldock PA, et al. Neuropeptide Y is expressed by osteocytes and can inhibit osteoblastic activity. J Cell Biochem. 2009;108(3):621–30.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  48. Fumoto T, Takeshita S, Ito M, Ikeda K. Physiological functions of osteoblast lineage and T cell-derived RANKL in bone homeostasis. J Bone Miner Res. 2014;29(4):830–42.

    Article  PubMed  CAS  Google Scholar 

  49. Xiong J, Piemontese M, Onal M, Campbell J, Goellner JJ, Dusevich V, et al. Osteocytes, not osteoblasts or lining cells, are the main source of the RANKL required for osteoclast formation in remodeling bone. PLoS ONE. 2015;10(9):e0138189.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  50. Bellido T, Ali AA, Gubrij I, Plotkin LI, Fu Q, O’Brien CA, et al. Chronic elevation of parathyroid hormone in mice reduces expression of sclerostin by osteocytes: a novel mechanism for hormonal control of osteoblastogenesis. Endocrinology. 2005;146(11):4577–83.

    Article  PubMed  CAS  Google Scholar 

  51. Lara-Castillo N, Kim-Weroha NA, Kamel MA, Javaheri B, Ellies DL, Krumlauf RE, et al. In vivo mechanical loading rapidly activates beta-catenin signaling in osteocytes through a prostaglandin mediated mechanism. Bone. 2015;76:58–66.

    Article  PubMed  CAS  Google Scholar 

  52. Brakspear K, Mason D. Glutamate signalling in bone. Front Endocrinol. 2012;3(89).

    Google Scholar 

  53. Huggett JF, Mustafa A, O’neal L, Mason DJ. The glutamate transporter GLAST-1 (EAAT-1) is expressed in the plasma membrane of osteocytes and is responsive to extracellular glutamate concentration. Biochem Soc Trans. 2002;30(Pt 6):890–3.

    Article  PubMed  CAS  Google Scholar 

  54. Mason DJ, Suva LJ, Genever PG, Patton AJ, Steuckle S, Hillam RA, et al. Mechanically regulated expression of a neural glutamate transporter in bone: a role for excitatory amino acids as osteotropic agents? Bone. 1997;20(3):199–205.

    Article  PubMed  CAS  Google Scholar 

  55. Szczesniak AM, Gilbert RW, Mukhida M, Anderson GI. Mechanical loading modulates glutamate receptor subunit expression in bone. Bone. 2005;37(1):63–73.

    Article  PubMed  CAS  Google Scholar 

  56. Nomura S, Takano-Yamamoto T. Molecular events caused by mechanical stress in bone. Matrix Biol. 2000;19(2):91–6.

    Article  PubMed  CAS  Google Scholar 

  57. Brady RT, O’Brien FJ, Hoey DA. Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation. Biochem Biophys Res Commun. 2015;459(1):118–23.

    Article  PubMed  CAS  Google Scholar 

  58. Norimatsu H, Yamamoto T, Ozawa H, Talmage RV. Changes in calcium phosphate on bone surfaces and in lining cells after the administration of parathyroid hormone or calcitonin. Clin Orthop Relat Res. 1982;164:271–8.

    PubMed  CAS  Google Scholar 

  59. Norimatsu H, Wiel CJ, Talmage RV. Morphological support of a role for cells lining bone surfaces in maintenance of plasma calcium concentration. Clin Orthop Relat Res. 1979;138:254–62.

    PubMed  Google Scholar 

  60. Mach DB, Rogers SD, Sabino MC, Luger NM, Schwei MJ, Pomonis JD, et al. Origins of skeletal pain: sensory and sympathetic innervation of the mouse femur. Neuroscience. 2002;113(1):155–66.

    Article  PubMed  CAS  Google Scholar 

  61. Allen MR, Hock JM, Burr DB. Periosteum: biology, regulation, and response to osteoporosis therapies. Bone. 2004;35(5):1003–12.

    Article  PubMed  CAS  Google Scholar 

  62. Chang MK, Raggatt LJ, Alexander KA, Kuliwaba JS, Fazzalari NL, Schroder K, et al. Osteal tissue macrophages are intercalated throughout human and mouse bone lining tissues and regulate osteoblast function in vitro and in vivo. J Immunol. 2008;181(2):1232–44.

    Article  PubMed  CAS  Google Scholar 

  63. Franz-Odendaal TA, Hall BK, Witten PE. Buried alive: how osteoblasts become osteocytes. Dev Dyn. 2006;235(1):176–90.

    Article  PubMed  CAS  Google Scholar 

  64. Sanchez-Ramos J, Song S, Cardozo-Pelaez F, Hazzi C, Stedeford T, Willing A, et al. Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp Neurol. 2000;164(2):247–56.

    Article  PubMed  CAS  Google Scholar 

  65. Chamberlain G, Fox J, Ashton B, Middleton J. Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells. 2007;25(11):2739–49.

    Article  PubMed  CAS  Google Scholar 

  66. Abdallah BM, Al-Shammary A, Skagen P, Abu DR, Adjaye J, Aldahmash A, et al. CD34 defines an osteoprogenitor cell population in mouse bone marrow stromal cells. Stem Cell Res. 2015;15(3):449–58.

    Article  PubMed  CAS  Google Scholar 

  67. Modder UI, Khosla S. Skeletal stem/osteoprogenitor cells: current concepts, alternate hypotheses, and relationship to the bone remodeling compartment. J Cell Biochem. 2008;103(2):393–400.

    Article  PubMed  CAS  Google Scholar 

  68. Addison WN, Fu MM, Yang HX, Lin Z, Nagano K, Gori F, et al. Direct transcriptional repression of Zfp423 by Zfp521 mediates a bone morphogenic protein-dependent osteoblast versus adipocyte lineage commitment switch. Mol Cell Biol. 2014;34(16):3076–85.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  69. Takarada-Iemata M, Takarada T, Nakamura Y, Nakatani E, Hori O, Yoneda Y. Glutamate preferentially suppresses osteoblastogenesis than adipogenesis through the cystine/glutamate antiporter in mesenchymal stem cells. J Cell Physiol. 2011;226(3):652–65.

    Article  PubMed  CAS  Google Scholar 

  70. Chang Y, Li H, Guo Z. Mesenchymal stem cell-like properties in fibroblasts. Cell Physiol Biochem. 2014;34(3):703–14.

    Article  PubMed  CAS  Google Scholar 

  71. Langevin HM, Cornbrooks CJ, Taatjes DJ. Fibroblasts form a body-wide cellular network. Histochem Cell Biol. 2004;122(1):7–15.

    Article  PubMed  CAS  Google Scholar 

  72. Yamamoto K, Kishida T, Sato Y, Nishioka K, Ejima A, Fujiwara H, et al. Direct conversion of human fibroblasts into functional osteoblasts by defined factors. Proc Natl Acad Sci USA. 2015;112(19):6152–7.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  73. Wu AC, Raggatt LJ, Alexander KA, Pettit AR. Unraveling macrophage contributions to bone repair. Bonekey Rep. 2013;2:373.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  74. Alexander KA, Chang MK, Maylin ER, Kohler T, Muller R, Wu AC, et al. Osteal macrophages promote in vivo intramembranous bone healing in a mouse tibial injury model. J Bone Miner Res. 2011;26(7):1517–32.

    Article  PubMed  CAS  Google Scholar 

  75. Hume DA, Loutit JF, Gordon S. The mononuclear phagocyte system of the mouse defined by immunohistochemical localization of antigen F4/80: macrophages of bone and associated connective tissue. J Cell Sci. 1984;66:189–94.

    PubMed  CAS  Google Scholar 

  76. Korolnek T, Hamza I. Macrophages and iron trafficking at the birth and death of red cells. Blood. 2015;125(19):2893–7.

    Article  PubMed  CAS  Google Scholar 

  77. Boisset JC, Robin C. On the origin of hematopoietic stem cells: progress and controversy. Stem Cell Res. 2012;8(1):1–13.

    Article  PubMed  CAS  Google Scholar 

  78. Mosaad YM. Hematopoietic stem cells: an overview. Transfus Apher Sci. 2014;51(3):68–82.

    Article  PubMed  Google Scholar 

  79. Nombela-Arrieta C, Pivarnik G, Winkel B, Canty KJ, Harley B, Mahoney JE, et al. Quantitative imaging of haematopoietic stem and progenitor cell localization and hypoxic status in the bone marrow microenvironment. Nat Cell Biol. 2013;15(5):533–43.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  80. Anthony BA, Link DC. Regulation of hematopoietic stem cells by bone marrow stromal cells. Trends Immunol. 2014;35(1):32–7.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  81. Millan JL. The role of phosphatases in the initiation of skeletal mineralization. Calcif Tissue Int. 2013;93(4):299–306.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  82. Zerega B, Cermelli S, Bianco P, Cancedda R, Cancedda FD. Parathyroid hormone [PTH(1-34)] and parathyroid hormone-related protein [PTHrP(1-34)] promote reversion of hypertrophic chondrocytes to a prehypertrophic proliferating phenotype and prevent terminal differentiation of osteoblast-like cells. J Bone Miner Res. 1999;14(8):1281–9.

    Article  PubMed  CAS  Google Scholar 

  83. Bianco P, Cancedda FD, Riminucci M, Cancedda R. Bone formation via cartilage models: the “borderline” chondrocyte. Matrix Biol. 1998;17(3):185–92.

    Article  PubMed  CAS  Google Scholar 

  84. Shapiro IM, Golub EE, Kakuta S, Hazelgrove J, Havery J, Chance B, et al. Initiation of endochondral calcification is related to changes in the redox state of hypertrophic chondrocytes. Science. 1982;217(4563):950–2.

    Article  PubMed  CAS  Google Scholar 

  85. Piepoli T, Mennuni L, Zerbi S, Lanza M, Rovati LC, Caselli G. Glutamate signaling in chondrocytes and the potential involvement of NMDA receptors in cell proliferation and inflammatory gene expression. Osteoarthritis Cartilage. 2009;17(8):1076–83.

    Article  PubMed  CAS  Google Scholar 

  86. Wang L, Hinoi E, Takemori A, Yoneda Y. Release of endogenous glutamate by AMPA receptors expressed in cultured rat costal chondrocytes. Biol Pharm Bull. 2005;28(6):990–3.

    Article  PubMed  CAS  Google Scholar 

  87. Wang L, Hinoi E, Takemori A, Nakamichi N, Yoneda Y. Glutamate inhibits chondral mineralization through apoptotic cell death mediated by retrograde operation of the cystine/glutamate antiporter. J Biol Chem. 2006;281(34):24553–65.

    Article  PubMed  CAS  Google Scholar 

  88. Islam A, Glomski C, Henderson ES. Endothelial cells and hematopoiesis: a light microscopic study of fetal, normal, and pathologic human bone marrow in plastic-embedded sections. Anat Rec. 1992;233(3):440–52.

    Article  PubMed  CAS  Google Scholar 

  89. Majesky MW, Dong XR, Hoglund V, Mahoney WM Jr, Daum G. The adventitia: a dynamic interface containing resident progenitor cells. Arterioscler Thromb Vasc Biol. 2011;31(7):1530–9.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  90. Edwards JR, Williams K, Kindblom LG, Meis-Kindblom JM, Hogendoorn PC, Hughes D, et al. Lymphatics and bone. Hum Pathol. 2008;39(1):49–55.

    Article  PubMed  Google Scholar 

  91. Masi L. Crosstalk between the brain and bone. Clin Cases Miner Bone Metab. 2012;9(1):13–6.

    PubMed Central  PubMed  Google Scholar 

  92. Serre CM, Farlay D, Delmas PD, Chenu C. Evidence for a dense and intimate innervation of the bone tissue, including glutamate-containing fibers. Bone. 1999;25(6):623–9.

    Article  PubMed  CAS  Google Scholar 

  93. Bataille C, Mauprivez C, Hay E, Baroukh B, Brun A, Chaussain C, et al. Different sympathetic pathways control the metabolism of distinct bone envelopes. Bone. 2012;50(5):1162–72.

    Article  PubMed  CAS  Google Scholar 

  94. Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker KL, et al. Leptin regulates bone formation via the sympathetic nervous system. Cell. 2002;111(3):305–17.

    Article  PubMed  CAS  Google Scholar 

  95. Jimenez-Andrade JM, Mantyh WG, Bloom AP, Xu H, Ferng AS, Dussor G, et al. A phenotypically restricted set of primary afferent nerve fibers innervate the bone versus skin: therapeutic opportunity for treating skeletal pain. Bone. 2010;46(2):306–13.

    Article  PubMed Central  PubMed  Google Scholar 

  96. Peters CM, Ghilardi JR, Keyser CP, Kubota K, Lindsay TH, Luger NM, et al. Tumor-induced injury of primary afferent sensory nerve fibers in bone cancer pain. Exp Neurol. 2005;193(1):85–100.

    Article  PubMed  Google Scholar 

  97. Hill EL, Turner R, Elde R. Effects of neonatal sympathectomy and capsaicin treatment on bone remodeling in rats. Neuroscience. 1991;44(3):747–55.

    Article  PubMed  CAS  Google Scholar 

  98. Jimenez-Andrade JM, Mantyh WG, Bloom AP, Freeman KT, Ghilardi JR, Kuskowski MA, et al. The effect of aging on the density of the sensory nerve fiber innervation of bone and acute skeletal pain. Neurobiol Aging. 2012;33(5):921–32.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  99. Sottnik JL, Campbell B, Mehra R, Behbahani-Nejad O, Hall CL, Keller ET. Osteocytes serve as a progenitor cell of osteosarcoma. J Cell Biochem. 2014;115(8):1420–9.

    Article  PubMed  CAS  Google Scholar 

  100. Lin PP, Wang Y, Lozano G. Mesenchymal stem cells and the origin of Ewing’s sarcoma. Sarcoma. 2011;2011.

    Google Scholar 

  101. Tanaka M, Yamazaki Y, Kanno Y, Igarashi K, Aisaki K, Kanno J, et al. Ewing’s sarcoma precursors are highly enriched in embryonic osteochondrogenic progenitors. J Clin Invest. 2014;124(7):3061–74.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  102. Pinder MA, Dibardino DJ, Collier AB, Knudson JD. Chondrosarcoma presenting with pulmonary embolism in a 9-year-old girl: a case report. Cardiol Young. 2015;25(2):384–7.

    Article  PubMed  Google Scholar 

  103. Rodriguez A, Roubertie F, Thumerel M, Jougon J. Pulmonary metastatic chondrosarcoma with massive extension into left atrium and left ventricle: outcome of surgical management in emergency. Eur J Cardiothorac Surg. 2013;44(5):e341–2.

    Article  PubMed  Google Scholar 

  104. Kyle RA, Rajkumar SV. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia. 2009;23(1):3–9.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  105. Coleman RE. Skeletal complications of malignancy. Cancer. 1997;80(8 Suppl):1588–94.

    Article  PubMed  CAS  Google Scholar 

  106. Paget S. The distribution of secondary growths in cancer of the breast. Lancet. 1889;29(1):571–3.

    Article  Google Scholar 

  107. Coleman RE. Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res. 2006;12(20 Pt 2):6243s–9s.

    Article  PubMed  Google Scholar 

  108. Oster G, Lamerato L, Glass AG, Richert-Boe KE, Lopez A, Chung K, et al. Natural history of skeletal-related events in patients with breast, lung, or prostate cancer and metastases to bone: a 15-year study in two large US health systems. Support Care Cancer. 2013;21(12):3279–86.

    Article  PubMed  Google Scholar 

  109. Gokaslan ZL, Aladag MA, Ellerhorst JA. Melanoma metastatic to the spine: a review of 133 cases. Melanoma Res. 2000;10(1):78–80.

    Article  PubMed  CAS  Google Scholar 

  110. Hartwich JE, Orr WS, Ng CY, Spence Y, McLaughlin JM, Furman WL, et al. Rapamycin increases neuroblastoma xenograft and host stromal derived osteoprotegerin inhibiting osteolytic bone disease in a bone metastasis model. J Pediatr Surg. 2013;48(1):47–55.

    Article  PubMed Central  PubMed  Google Scholar 

  111. DiSibio G, French SW. Metastatic patterns of cancers: results from a large autopsy study. Arch Pathol Lab Med 2008;132(6):931–9.

    Google Scholar 

  112. Zhang M, Sun J. Bone metastasis from ovarian cancer. clinical analysis of 26 cases. Saudi Med J. 2013;34(12):1270–3.

    PubMed  CAS  Google Scholar 

  113. Sehouli J, Olschewski J, Schotters V, Fotopoulou C, Pietzner K. Prognostic role of early versus late onset of bone metastasis in patients with carcinoma of the ovary, peritoneum and fallopian tube. Ann Oncol. 2013;24(12):3024–8.

    Article  PubMed  CAS  Google Scholar 

  114. Hillner BE, Ingle JN, Chlebowski RT, Gralow J, Yee GC, Janjan NA, et al. American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol. 2003;21(21):4042–57.

    Article  PubMed  CAS  Google Scholar 

  115. Coleman R, Body JJ, Aapro M, Hadji P, Herrstedt J. Bone health in cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol. 2014;25(Suppl 3):iii124–iii137.

    Google Scholar 

  116. He J, Liu Z, Zheng Y, Qian J, Li H, Lu Y, et al. p38 MAPK in myeloma cells regulates osteoclast and osteoblast activity and induces bone destruction. Cancer Res. 2012;72(24):6393–402.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  117. Choi B, Lee EJ, Song DH, Yoon SC, Chung YH, Jang Y, et al. Elevated Pentraxin 3 in bone metastatic breast cancer is correlated with osteolytic function. Oncotarget. 2014;5(2):481–92.

    Article  PubMed Central  PubMed  Google Scholar 

  118. Gartrell BA, Coleman R, Efstathiou E, Fizazi K, Logothetis CJ, Smith MR, et al. Metastatic prostate cancer and the bone: significance and therapeutic options. Eur Urol. 2015;68(5):850–8.

    Article  PubMed  Google Scholar 

  119. Mathew A, Brufsky A. Bisphosphonates in breast cancer. Int J Cancer. 2015;137(4):753–64.

    Article  PubMed  CAS  Google Scholar 

  120. Granchi D, Baglio SR, Amato I, Giunti A, Baldini N. Paracrine inhibition of osteoblast differentiation induced by neuroblastoma cells. Int J Cancer. 2008;123(7):1526–35.

    Article  PubMed  CAS  Google Scholar 

  121. Lee JW, Chung HY, Ehrlich LA, Jelinek DF, Callander NS, Roodman GD, et al. IL-3 expression by myeloma cells increases both osteoclast formation and growth of myeloma cells. Blood. 2004;103(6):2308–15.

    Article  PubMed  CAS  Google Scholar 

  122. Ehrlich LA, Chung HY, Ghobrial I, Choi SJ, Morandi F, Colla S, et al. IL-3 is a potential inhibitor of osteoblast differentiation in multiple myeloma. Blood. 2005;106(4):1407–14.

    Article  PubMed  CAS  Google Scholar 

  123. McCoy EM, Hong H, Pruitt HC, Feng X. IL-11 produced by breast cancer cells augments osteoclastogenesis by sustaining the pool of osteoclast progenitor cells. BMC Cancer. 2013;13:16.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  124. Fromigue O, Kheddoumi N, Lomri A, Marie PJ, Body JJ. Breast cancer cells release factors that induced apoptosis in human bone marrow stromal cells. J Bone Miner Res. 2001;16(9):1600–10.

    Article  PubMed  CAS  Google Scholar 

  125. Ibrahim T, Flamini E, Mercatali L, Sacanna E, Serra P, Amadori D. Pathogenesis of osteoblastic bone metastases from prostate cancer. Cancer. 2010;116(6):1406–18.

    Article  PubMed  CAS  Google Scholar 

  126. Roudier MP, Morrissey C, True LD, Higano CS, Vessella RL, Ott SM. Histopathological assessment of prostate cancer bone osteoblastic metastases. J Urol. 2008;180(3):1154–60.

    Article  PubMed Central  PubMed  Google Scholar 

  127. Seeman E. Bone quality: the material and structural basis of bone strength. J Bone Miner Metab. 2008;26(1):1–8.

    Article  PubMed  Google Scholar 

  128. Larson SR, Chin J, Zhang X, Brown LG, Coleman IM, Lakely B, et al. Prostate cancer derived prostatic acid phosphatase promotes an osteoblastic response in the bone microenvironment. Clin Exp Metastasis. 2014;31(2):247–56.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  129. Rabbani SA, Desjardins J, Bell AW, Banville D, Mazar A, Henkin J, et al. An amino-terminal fragment of urokinase isolated from a prostate cancer cell line (PC-3) is mitogenic for osteoblast-like cells. Biochem Biophys Res Commun. 1990;173(3):1058–64.

    Article  PubMed  CAS  Google Scholar 

  130. Seidlitz EP, Sharma MK, Singh G. Extracellular glutamate alters mature osteoclast and osteoblast functions. Can J Physiol Pharmacol. 2010;88(9):929–36.

    Article  PubMed  CAS  Google Scholar 

  131. Alam AS, Gallagher A, Shankar V, Ghatei MA, Datta HK, Huang CL, et al. Endothelin inhibits osteoclastic bone resorption by a direct effect on cell motility: implications for the vascular control of bone resorption. Endocrinology. 1992;130(6):3617–24.

    PubMed  CAS  Google Scholar 

  132. Liu F, Shen W, Qiu H, Hu X, Zhang C, Chu T. Prostate cancer cells induce osteoblastic differentiation via semaphorin 3A. Prostate. 2015;75(4):370–80.

    Article  PubMed  CAS  Google Scholar 

  133. Chiao JW, Moonga BS, Yang YM, Kancherla R, Mittelman A, Wu-Wong JR, et al. Endothelin-1 from prostate cancer cells is enhanced by bone contact which blocks osteoclastic bone resorption. Br J Cancer. 2000;83(3):360–5.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  134. Yin JJ, Mohammad KS, Kakonen SM, Harris S, Wu-Wong JR, Wessale JL, et al. A causal role for endothelin- in the pathogenesis of osteoblastic bone metastases. Proc Natl Acad Sci USA. 2003;100(19):10954–9.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  135. Udagawa N, Takahashi N, Jimi E, Matsuzaki K, Tsurukai T, Itoh K, et al. Osteoblasts/stromal cells stimulate osteoclast activation through expression of osteoclast differentiation factor/RANKL but not macrophage colony-stimulating factor: receptor activator of NF-kappa B ligand. Bone. 1999;25(5):517–23.

    Article  PubMed  CAS  Google Scholar 

  136. Udagawa N, Takahashi N, Yasuda H, Mizuno A, Itoh K, Ueno Y, et al. Osteoprotegerin produced by osteoblasts is an important regulator in osteoclast development and function. Endocrinology. 2000;141(9):3478–84.

    PubMed  CAS  Google Scholar 

  137. Keller ET, Brown J. Prostate cancer bone metastases promote both osteolytic and osteoblastic activity. J Cell Biochem. 2004;91(4):718–29.

    Article  PubMed  CAS  Google Scholar 

  138. Bunyaratavej P, Hullinger TG, Somerman MJ. Bone morphogenetic proteins secreted by breast cancer cells upregulate bone sialoprotein expression in preosteoblast cells. Exp Cell Res. 2000;260(2):324–33.

    Article  PubMed  CAS  Google Scholar 

  139. Kassen D, Moore S, Percy L, Herledan G, Bounds D, Rodriguez-Justo M, et al. The bone marrow stromal compartment in multiple myeloma patients retains capability for osteogenic differentiation in vitro: defining the stromal defect in myeloma. Br J Haematol. 2014;167(2):194–206.

    Article  PubMed  CAS  Google Scholar 

  140. Seidlitz EP, Sharma MK, Singh G. A by-product of glutathione production in cancer cells may cause disruption in bone metabolic processes. Can J Physiol Pharmacol. 2010;88(3):197–203.

    Article  PubMed  CAS  Google Scholar 

  141. Lieben L, Carmeliet G. The delicate balance between vitamin D, calcium and bone homeostasis: lessons learned from intestinal- and osteocyte-specific VDR null mice. J Steroid Biochem Mol Biol. 2013;136:102–6.

    Article  PubMed  CAS  Google Scholar 

  142. Masuyama R. Role of local vitamin D signaling and cellular calcium transport system in bone homeostasis. J Bone Miner Metab. 2014;32(1):1–9.

    Article  PubMed  CAS  Google Scholar 

  143. Lieben L, Carmeliet G, Masuyama R. Calcemic actions of vitamin D: effects on the intestine, kidney and bone. Best Pract Res Clin Endocrinol Metab. 2011;25(4):561–72.

    Article  PubMed  CAS  Google Scholar 

  144. Hewer W, Stark HW. Psychiatric disorders in elderly patients caused by disturbed calcium metabolism. Fortschr Neurol Psychiatr. 2010;78(3):161–7.

    Article  PubMed  CAS  Google Scholar 

  145. Babar G, Alemzadeh R. A case of acute psychosis in an adolescent male. Case Rep Endocrinol. 2014;2014:937631.

    PubMed Central  PubMed  Google Scholar 

  146. Bergwitz C, Juppner H. Regulation of phosphate homeostasis by PTH, vitamin D, and FGF23. Annu Rev Med. 2010;61:91–104.

    Article  PubMed  CAS  Google Scholar 

  147. Lederer E. Regulation of serum phosphate. J Physiol. 2014;592(Pt 18):3985–95.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  148. Hautmann AH, Hautmann MG, Kolbl O, Herr W, Fleck M. Tumor-induced osteomalacia: an up-to-date review. Curr Rheumatol Rep. 2015;17(6):512.

    Article  PubMed  CAS  Google Scholar 

  149. Dallas SL, Rosser JL, Mundy GR, Bonewald LF. Proteolysis of latent transforming growth factor-beta (TGF-beta)-binding protein-1 by osteoclasts. A cellular mechanism for release of TGF-beta from bone matrix. J Biol Chem. 2002;277(24):21352–60.

    Article  PubMed  CAS  Google Scholar 

  150. Pfeilschifter J, Bonewald L, Mundy GR. Characterization of the latent transforming growth factor beta complex in bone. J Bone Miner Res. 1990;5(1):49–58.

    Article  PubMed  CAS  Google Scholar 

  151. Meng X, Vander AA, Lee P, Hostetter G, Bhowmick NA, Matrisian LM, et al. Myeloid-specific TGF-beta signaling in bone promotes basic-FGF and breast cancer bone metastasis. Oncogene. 2015.

    Google Scholar 

  152. Ota K, Quint P, Ruan M, Pederson L, Westendorf JJ, Khosla S, et al. TGF-beta induces Wnt10b in osteoclasts from female mice to enhance coupling to osteoblasts. Endocrinology. 2013;154(10):3745–52.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  153. Duivenvoorden WC, Popovic SV, Lhotak S, Seidlitz E, Hirte HW, Tozer RG, et al. Doxycycline decreases tumor burden in a bone metastasis model of human breast cancer. Cancer Res. 2002;62(6):1588–91.

    PubMed  CAS  Google Scholar 

  154. Saikali Z, Singh G. Doxycycline and other tetracyclines in the treatment of bone metastasis. Anticancer Drugs. 2003;14(10):773–8.

    Article  PubMed  CAS  Google Scholar 

  155. Seidlitz E, Saikali Z, Singh G. Use of tetracyclines for bone metastases. In: Singh G, Rabbani S, editors. Bone metastasis: experimental and clinical therapeutics. Totowa: Humana Press Inc.; 2005. p. 295–305.

    Google Scholar 

  156. Casbon AJ, Reynaud D, Park C, Khuc E, Gan DD, Schepers K, et al. Invasive breast cancer reprograms early myeloid differentiation in the bone marrow to generate immunosuppressive neutrophils. Proc Natl Acad Sci USA. 2015;112(6):E566–75.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  157. Schepers K, Pietras EM, Reynaud D, Flach J, Binnewies M, Garg T, et al. Myeloproliferative neoplasia remodels the endosteal bone marrow niche into a self-reinforcing leukemic niche. Cell Stem Cell. 2013;13(3):285–99.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  158. Young MR, Wright MA, Coogan M, Young ME, Bagash J. Tumor-derived cytokines induce bone marrow suppressor cells that mediate immunosuppression through transforming growth factor beta. Cancer Immunol Immunother. 1992;35(1):14–8.

    Article  PubMed  CAS  Google Scholar 

  159. Ho ML, Tsai TN, Chang JK, Shao TS, Jeng YR, Hsu C. Down-regulation of N-methyl D-aspartate receptor in rat-modeled disuse osteopenia. Osteoporos Int. 2005;16(12):1780–8.

    Article  PubMed  CAS  Google Scholar 

  160. Cowan RW, Seidlitz EP, Singh G. Glutamate signalling in healthy and diseased bone. Front Endocrinol. 2012;3(89):1–7.

    Google Scholar 

  161. Ungard RG, Seidlitz EP, Singh G. Inhibition of breast cancer-cell glutamate release with sulfasalazine limits cancer-induced bone pain. Pain. 2014;155(1):28–36.

    Article  PubMed  CAS  Google Scholar 

  162. Marwaha RK, Kulkarni KP, Bansal D, Trehan A. Acute lymphoblastic leukemia masquerading as juvenile rheumatoid arthritis: diagnostic pitfall and association with survival. Ann Hematol. 2010;89(3):249–54.

    Article  PubMed  CAS  Google Scholar 

  163. Kaur P, Shah BS, Baja P. Multiple myeloma: a clinical and pathological profile. Gulf J Oncolog. 2014;1(16):14–20.

    PubMed  CAS  Google Scholar 

  164. Castel LD, Abernethy AP, Li Y, Depuy V, Saville BR, Hartmann KE. Hazards for pain severity and pain interference with daily living, with exploration of brief pain inventory cutpoints, among women with metastatic breast cancer. J Pain Symptom Manage. 2007;34(4):380–92.

    Article  PubMed  Google Scholar 

  165. Eaton CL, Coleman RE. Pathophysiology of bone metastases from prostate cancer and the role of bisphosphonates in treatment. Cancer Treat Rev. 2003;29(3):189–98.

    Article  PubMed  CAS  Google Scholar 

  166. Nagae M, Hiraga T, Yoneda T. Acidic microenvironment created by osteoclasts causes bone pain associated with tumor colonization. J Bone Miner Metab. 2007;25(2):99–104.

    Article  PubMed  Google Scholar 

  167. Yoneda T, Hiasa M, Nagata Y, Okui T, White F. Contribution of acidic extracellular microenvironment of cancer-colonized bone to bone pain. Biochim Biophys Acta. 2015;1848(10 Pt B):2677–84.

    Google Scholar 

  168. Cleeland CS, Body JJ, Stopeck A, von MR, Fallowfield L, Mathias SD, et al. Pain outcomes in patients with advanced breast cancer and bone metastases: results from a randomized, double-blind study of denosumab and zoledronic acid. Cancer. 2013;119(4):832–8.

    Google Scholar 

  169. Sample SJ, Heaton CM, Behan M, Bleedorn JA, Racette MA, Hao Z, et al. Role of calcitonin gene-related peptide in functional adaptation of the skeleton. PLoS ONE. 2014;9(12):e113959.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  170. Rusz O, Kahan Z. Bone homeostasis and breast cancer: implications for complex therapy and the maintenance of bone integrity. Pathol Oncol Res. 2013;19(1):1–10.

    Article  PubMed  CAS  Google Scholar 

  171. Mundy GR. Mechanisms of bone metastasis. Cancer. 1997;80(8 Suppl):1546–56.

    Article  PubMed  CAS  Google Scholar 

  172. Kakonen SM, Mundy GR. Mechanisms of osteolytic bone metastases in breast carcinoma. Cancer. 2003;97(3 Suppl):834–9.

    Article  PubMed  Google Scholar 

  173. Reddi AH, Roodman D, Freeman C, Mohla S. Mechanisms of tumor metastasis to the bone: challenges and opportunities. J Bone Miner Res. 2003;18(2):190–4.

    Article  PubMed  CAS  Google Scholar 

  174. Chirgwin JM, Mohammad KS, Guise TA. Tumor-bone cellular interactions in skeletal metastases. J Musculoskelet Neuronal Interact. 2004;4(3):308–18.

    PubMed  CAS  Google Scholar 

  175. Fournier PG, Chirgwin JM, Guise TA. New insights into the role of T cells in the vicious cycle of bone metastases. Curr Opin Rheumatol. 2006;18(4):396–404.

    Article  PubMed  CAS  Google Scholar 

  176. Schell MJ. The N-methyl D-aspartate receptor glycine site and D-serine metabolism: an evolutionary perspective. Philos Trans R Soc Lond B Biol Sci. 2004;359(1446):943–64.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  177. Seidlitz EP, Sharma MK, Saikali Z, Ghert M, Singh G. Cancer cell lines release glutamate into the extracellular environment. Clin Exp Metastasis. 2009;26(7):781–7.

    Article  PubMed  CAS  Google Scholar 

  178. Aldridge SE, Lennard TW, Williams JR, Birch MA. Vascular endothelial growth factor acts as an osteolytic factor in breast cancer metastases to bone. Br J Cancer. 2005;92(8):1531–7.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  179. Ghilardi JR, Freeman KT, Jimenez-Andrade JM, Mantyh WG, Bloom AP, Kuskowski MA, et al. Administration of a tropomyosin receptor kinase inhibitor attenuates sarcoma-induced nerve sprouting, neuroma formation and bone cancer pain. Mol Pain. 2010;6(1):87.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  180. Iversen PO, Wiig H. Tumor necrosis factor alpha and adiponectin in bone marrow interstitial fluid from patients with acute myeloid leukemia inhibit normal hematopoiesis. Clin Cancer Res. 2005;11(19 Pt 1):6793–9.

    Article  PubMed  CAS  Google Scholar 

  181. Nakamura T, Hanada K, Tamura M, Shibanushi T, Nigi H, Tagawa M, et al. Stimulation of endosteal bone formation by systemic injections of recombinant basic fibroblast growth factor in rats. Endocrinology. 1995;136(3):1276–84.

    PubMed  CAS  Google Scholar 

  182. Huang W, Fridman Y, Bonfil RD, Ustach CV, Conley-LaComb MK, Wiesner C, et al. A novel function for platelet-derived growth factor D: induction of osteoclastic differentiation for intraosseous tumor growth. Oncogene. 2012;31(42):4527–35.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  183. Mohan S, Baylink DJ. Bone growth factors. Clin Orthop Relat Res. 1991;263:30–48.

    PubMed  Google Scholar 

  184. Thomas RJ, Guise TA, Yin JJ, Elliott J, Horwood NJ, Martin TJ, et al. Breast cancer cells interact with osteoblasts to support osteoclast formation. Endocrinology. 1999;140(10):4451–8.

    PubMed  CAS  Google Scholar 

  185. Soki FN, Park SI, McCauley LK. The multifaceted actions of PTHrP in skeletal metastasis. Future Oncol. 2012;8(7):803–17.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  186. Guo Y, Tiedemann K, Khalil JA, Russo C, Siegel PM, Komarova SV. Osteoclast precursors acquire sensitivity to breast cancer derived factors early in differentiation. Bone. 2008;43(2):386–93.

    Article  PubMed  CAS  Google Scholar 

  187. Lee Y, Schwarz E, Davies M, Jo M, Gates J, Wu J, et al. Differences in the cytokine profiles associated with prostate cancer cell induced osteoblastic and osteolytic lesions in bone. J Orthop Res. 2003;21(1):62–72.

    Article  PubMed  CAS  Google Scholar 

  188. Saad F, Markus R, Goessl C. Targeting the receptor activator of nuclear factor-kappaB (RANK) ligand in prostate cancer bone metastases. BJU Int. 2008;101(9):1071–5.

    Article  PubMed  CAS  Google Scholar 

  189. Sugatani T, Hruska KA. MicroRNA-223 is a key factor in osteoclast differentiation. J Cell Biochem. 2007;101(4):996–9.

    Article  PubMed  CAS  Google Scholar 

  190. Sugatani T, Hruska KA. Impaired micro-RNA pathways diminish osteoclast differentiation and function. J Biol Chem. 2009;284(7):4667–78.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  191. Ell B, Mercatali L, Ibrahim T, Campbell N, Schwarzenbach H, Pantel K, et al. Tumor-induced osteoclast miRNA changes as regulators and biomarkers of osteolytic bone metastasis. Cancer Cell. 2013;24(4):542–56.

    Article  PubMed  CAS  Google Scholar 

  192. De Winter F, Vo T, Stam FJ, Wisman LA, Bar PR, Niclou SP, et al. The expression of the chemorepellent Semaphorin 3A is selectively induced in terminal Schwann cells of a subset of neuromuscular synapses that display limited anatomical plasticity and enhanced vulnerability in motor neuron disease. Mol Cell Neurosci. 2006;32(1–2):102–17.

    Article  PubMed  CAS  Google Scholar 

  193. Peng Y, Li Z, Li Z. GRP78 secreted by tumor cells stimulates differentiation of bone marrow mesenchymal stem cells to cancer-associated fibroblasts. Biochem Biophys Res Commun. 2013;440(4):558–63.

    Article  PubMed  CAS  Google Scholar 

  194. Smadja DM, d’Audigier C, Weiswald LB, Badoual C, Dangles-Marie V, Mauge L, et al. The Wnt antagonist Dickkopf-1 increases endothelial progenitor cell angiogenic potential. Arterioscler Thromb Vasc Biol. 2010;30(12):2544–52.

    Article  PubMed  CAS  Google Scholar 

  195. Xu W, Liu LZ, Loizidou M, Ahmed M, Charles IG. The role of nitric oxide in cancer. Cell Res. 2002;12(5–6):311–20.

    Article  PubMed  Google Scholar 

  196. Yuan FL, Wang HR, Zhao MD, Yuan W, Cao L, Duan PG, et al. Ovarian cancer G protein-coupled receptor 1 is involved in acid-induced apoptosis of endplate chondrocytes in intervertebral discs. J Bone Miner Res. 2014;29(1):67–77.

    Article  PubMed  CAS  Google Scholar 

  197. Walker K, Medhurst SJ, Kidd BL, Glatt M, Bowes M, Patel S, et al. Disease modifying and anti-nociceptive effects of the bisphosphonate, zoledronic acid in a model of bone cancer pain. Pain. 2002;100(3):219–29.

    Article  PubMed  CAS  Google Scholar 

  198. Yoneda T, Hata K, Nakanishi M, Nagae M, Nagayama T, Wakabayashi H, et al. Involvement of acidic microenvironment in the pathophysiology of cancer-associated bone pain. Bone. 2011;48(1):100–5.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gurmit Singh .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Seidlitz, E., Popovic, S., Clemons, M., Singh, G. (2016). Oncodynamic Changes in Skeleton. In: Singh, G. (eds) Oncodynamics: Effects of Cancer Cells on the Body. Springer, Cham. https://doi.org/10.1007/978-3-319-28558-0_9

Download citation

Publish with us

Policies and ethics