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Metastatic Disease to the Musculoskeletal System

  • David G. Hicks
Part of the Current Clinical Oncology book series (CCO)

Abstract

Bone is a dynamic tissue that undergoes continuous remodeling. It goes through a balanced process that entails repeated cycles of bone resorption coupled with synthesis of new bone matrix (Fig. 1). These remodeling cycles are influenced by an individual’s age, endocrine and nutritional status, and level of physical activity. This ongoing tissue turnover is important for meeting the often conflicting need of the skeleton to maintain structural support for the body while also providing a source of ions for mineral homeostasis. The maintenance of skeletal mass in the face of continuous bone remodeling requires the coordinated activities of osteoblasts and osteoclasts, the two cell types responsible for skeletal matrix formation and resorption (1) (Fig. 1). Advances in our understanding of the precise mechanisms that control the cellular interactions and coupled activities of these two cell types have provided new insight into a number of diseases affecting the skeleton. These disorders are characterized by an imbalance of remodeling with subsequent increase in bone resorption, decreased bone mass, and loss of skeletal stability and integrity. This is particularly true for neoplastic diseases, in which a number of common human malignancies have a propensity to spread to the skeleton, resulting in significant morbidity and mortality from bone destruction (2).

Keywords

Breast Cancer Bone Resorption Bone Metastasis Bone Remodel Bone Matrix 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Masi L, Brandi ML. Physiopathological basis of bone turnover. Q J Nucl Med 2001; 45:2–6.PubMedGoogle Scholar
  2. 2.
    Coleman RE. Skeletal complications of malignancy. Cancer 1997; 80:1588–1594.PubMedCrossRefGoogle Scholar
  3. 3.
    Rodan GA, Martin TJ. Therapeutic approaches to bone diseases. Science 2000; 289:1508–1514.PubMedCrossRefGoogle Scholar
  4. 4.
    Goltzman D. Osteolysis and cancer. J Clin Invest 2001; 107:1219–1220.PubMedCrossRefGoogle Scholar
  5. 5.
    Taube T, Elomaa I, Blomqvist C, Beneton MN, Kanis JA. Histomorphometric evidence for osteoclast-mediated bone resorption in metastatic breast cancer. Bone 1994; 15:161–166.PubMedCrossRefGoogle Scholar
  6. 6.
    Guise TA. Molecular mechanisms of osteolytic bone metastases. Cancer 2000; 88:2892–2898.PubMedCrossRefGoogle Scholar
  7. 7.
    Paget S. The distribution of secondary growths in cancer of the breast. Lancet 1889; 1:571–572.CrossRefGoogle Scholar
  8. 8.
    Martin TJ, Moseley JM. Mechanisms in the skeletal complications of breast cancer. Endocr Relat Cancer 2000; 7:271–284.PubMedCrossRefGoogle Scholar
  9. 9.
    Harvery HA. Issues concerning the role of chemotherapy and hormonal thereapy of bone metastases from breast carcinoma. Cancer 1997; 80:1646–1651.CrossRefGoogle Scholar
  10. 10.
    Domchek SM, Younger J, Finkelstein DM, Seiden MV. Predictors of skeletal complications in patients with metastatic breast carcinoma. Cancer 2000; 89:363–368.PubMedCrossRefGoogle Scholar
  11. 11.
    Carlin BI, Andriole GL. The natural history, skeletal complications, and management of bone metastases in patients with prostate carcinoma. Cancer 2000; 88:2989–2994.PubMedCrossRefGoogle Scholar
  12. 12.
    Berruti A, Dogliotti L, Bitossi R, et al. Incidence of skeletal complications in patients with bone metastatic prostate cancer and hormone refractory disease: predictive role of bone resorption and formation markers evaluated at baseline. J Urol 2000; 164:1248–1253.PubMedCrossRefGoogle Scholar
  13. 13.
    Whitmore WJ. Natural history and staging of prostate cancer. Urol Clin North Am 1984; 11:209–220.Google Scholar
  14. 14.
    Russell G, Mueller G, Shipman C, Croucher P. Clinical disorders of bone resorption. Novartis Found Symp 2001 232:251–267; discussion 267–271.PubMedCrossRefGoogle Scholar
  15. 15.
    Teitelbaum SL. Bone resorption by osteoclasts. Science 2000; 289:1504–1508.PubMedCrossRefGoogle Scholar
  16. 16.
    Athanasou NA, Sabokbar A. Human osteoclast ontogeny and pathological bone resorption. Histol Histopathol 1999; 14:635–647.PubMedGoogle Scholar
  17. 17.
    McHugh KP, Hodivala-Dilke K, Zheng MH, et al. Mice lacking beta3 integrins are osteosclerotic because of dysfunctional osteoclasts. J Clin Invest 2000; 105:433–440.PubMedCrossRefGoogle Scholar
  18. 18.
    Teitelbaum SL, Tondravi MM, Ross FP. Osteoclasts, macrophages, and the molecular mechanisms of bone resorption. J Leukoc Biol 1997; 61:381–388.PubMedGoogle Scholar
  19. 19.
    Mundy GR. Bone-resorbing cells. In: Favus MJ ed. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 3rd ed. Philadelphia, PA: Lippincott-Raven; 1996:16–24.Google Scholar
  20. 20.
    Hughes DE, Wright KR, Uy HL, et al. Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. J Bone Miner Res 1995; 10:1478–1487.PubMedGoogle Scholar
  21. 21.
    Canalis E. Regulation of bone remodeling. In: Favus MJ ed. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 3rd ed. Philadelphia, PA: Lippincott-Raven; 1996:29–34.Google Scholar
  22. 22.
    Hauschka PV, Mavrakos AE, Iafrati MD, Doleman SE, Klagsburn M. Growth factors in bone matrix: isolation of multiple types by affinity chromatography on heparin-sepharose. J Biol Chem 1986; 261:12,665–12,674.PubMedGoogle Scholar
  23. 23.
    Bautista CM, Mohan S, Baylink DJ. Insulin-like growth factors I and II are present in the skeletal tissue of ten vertebrates. Metabolism 1990; 39:96–100.PubMedCrossRefGoogle Scholar
  24. 24.
    Orr FW, Lee J, Duivenvoorden WC, Singh G. Pathophysiologic interactions in skeletal metastasis. Cancer 2000; 88:2912–2918.PubMedCrossRefGoogle Scholar
  25. 25.
    Boyce BF, Huges DE, Wright KR, Xing L, Dai A. Recent advances in bone biology provide insights into the pathogensis of bone disease. Lab Invest 1999; 79:83–94.PubMedGoogle Scholar
  26. 26.
    Chambers TJ. Regulation of the differentiation and function of osteoclasts. J Pathol 2000; 192:4–13.PubMedCrossRefGoogle Scholar
  27. 27.
    Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT, Martin TJ. Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev 1999; 20:345–357.PubMedCrossRefGoogle Scholar
  28. 28.
    Hofbauer LC, Khosla S, Dunstan CR, Lacey DL, Boyle WJ, Riggs BL. The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption. J Bone Miner Res 2000; 15:2–12.PubMedCrossRefGoogle Scholar
  29. 29.
    Takahashi N, Udagawa N, Suda T. A new member of tumor necrosis factor ligand family, ODF/OPGL/TRANCE/RANKL, regulates osteoclast differentiation and function. Biochem Biophys Res Commun 1999; 256:449–455.PubMedCrossRefGoogle Scholar
  30. 30.
    Kong YY, Boyle WJ, Penninger JM. Osteoprotegerin ligand: a common link between osteoclastogenesis, lymph node formation and lymphocyte development. Immunol Cell Biol 1999; 77:188–193.PubMedCrossRefGoogle Scholar
  31. 31.
    Anderson DM, Maraskovsky E, Billingsley WL, et al. A homologue of the TNF receptor and its lignad enhance T-cell growth and dentritic-cell function. Nature 1997; 390:175–179.PubMedCrossRefGoogle Scholar
  32. 32.
    Simonet WS, Lacey DL, Dunstan CR, et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 1997; 89:309–319.PubMedCrossRefGoogle Scholar
  33. 33.
    Puzas JE. Osteoblast cell biology-lineage and function. In: Favus MJ ed. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 3rd ed. Philadelphia, PA: Lippincott-Raven; 1996:29–34.Google Scholar
  34. 34.
    Woodhouse EC, Chuaqui F, Liotta LA. General mechanisms of metastasis. Cancer 1997; 80:1529–1537.PubMedCrossRefGoogle Scholar
  35. 35.
    Nicolson GL. Organ specificity of tumor metastasis: role of preferential adhesion, invasion and growth of malignant cells at specific secondary sites. Cancer Metastasis Rev 1988; 7:143–188.PubMedCrossRefGoogle Scholar
  36. 36.
    Cumming J, Hacking N, Fairhurst J, Ackery D, Jenkins JD. Distribution of bony metastases in prostatic carcinoma. Br J Urol 1990; 66:411–414.PubMedCrossRefGoogle Scholar
  37. 37.
    Nishijima Y, Koiso K, Nemoto R. The role of the vertebral veins in the dissemination of prostate carcinoma. Nippon Hinyokika Gakkai Zasshi 1995; 86:927–932.PubMedGoogle Scholar
  38. 38.
    Batson OV. The function of the vertebral veins and their role in the spread of metastases. 1940; Ann Surg 112:138.PubMedCrossRefGoogle Scholar
  39. 39.
    Goltzman D. Mechanisms of the development of osteoblastic metastases. Cancer 1997; 80:1581–1587.PubMedCrossRefGoogle Scholar
  40. 40.
    Arguello F, Baggs RB, Frantz CN. A murine model of experimental metastasis to bone and bone marrow. Cancer Res 1988; 48:6876–6881.PubMedGoogle Scholar
  41. 41.
    Haq M, Goltzman D, Tremblay G, Brodt P. Rat prostate adenocarcimoma cells disseminate to bone and adhere preferentially to bone marrow-derived endothelial cells. Cancer Res 1992; 52:4613–4619.PubMedGoogle Scholar
  42. 42.
    Gasparini G. Clinical significance of the determination of angiogenesis in human breast cancer: update of the biological background and overview of the vicenza studies. Eur J Cancer 1996; 32A:2485–2493.PubMedCrossRefGoogle Scholar
  43. 43.
    Karaiossifidi H, Kouri E, Arvaniti H, Sfikas S, Vasilaros S. Tumor angiogenesis in node-negative breast cancer: relationship with lapse free survival. Anticancer Res 1996; 16:4001–4002.PubMedGoogle Scholar
  44. 44.
    Heimann R, Ferguson D, Powers C, Recant WM, Weichselbaum RR, Hellman S. Angiogenesis as a predictor of long-term survival for patients with node-negative breast cancer. J Natl Cancer Inst 1996; 88:1764–1769.PubMedCrossRefGoogle Scholar
  45. 45.
    Silberman MA, Partin AW, Veltri RW, Epstein JI. Tumor angiogenesis correlates with progression after radical prostatectomy but not with pathologic stage in Gleason sum 5 to 7 adenocarcinoma of the prostate. Cancer 1996; 79:772–779.CrossRefGoogle Scholar
  46. 46.
    Saaristo A, Karpanen T, Alitalo K. Mechanisms of angiogenesis and their use in the inhibition of tumor growth and metastasis. Oncogene 2000; 19:6122–6129.PubMedCrossRefGoogle Scholar
  47. 47.
    Denijn M, Ruiter DJ. The possible role of angiogenesis in the metastatic potential of human melanoma: clinicopathological aspects. Melanoma Res 1993; 3:5–14.PubMedCrossRefGoogle Scholar
  48. 48.
    Huang S, Pettaway CA, Uehara H, Bucana CD, Fidler IJ. Blockade of NF-kB activity in human prostate cancer cells is associated with suppression of angiogenesis, invasion and metastasis. Oncogene 2001; 20:4188–4197.PubMedCrossRefGoogle Scholar
  49. 49.
    Haggstrom S, Bergh A, Damber JE. Vascular endothelial growth factor content in metastasizing and nonmetastasizing Dunning prostatic adenocarcinoma. Prostate 2000; 45:42–50.PubMedCrossRefGoogle Scholar
  50. 50.
    Winding B, Misander H, Sveigaard B, et al. Human breast cancer cells induced angiogenesis, recruitment, and activation of osteoclasts in osteolytic metastasis. J Cancer Res Clin Oncol 2000; 126:631–640.PubMedCrossRefGoogle Scholar
  51. 51.
    McGowan NW, Walker EJ, Macpherson H, Ralston SH, Helfrich MH. Cytokine-activated endothelium recruits osteoclast precursors. Endocrinology 2001; 142:1678–1681.PubMedCrossRefGoogle Scholar
  52. 52.
    Mundy GR. Mechanisms of bone metastasis. Cancer 1997; 80:1546–1556.PubMedCrossRefGoogle Scholar
  53. 53.
    Albelda SM, Buck CA. Integrins and other cell adhesion molecules. FASEB 1990; 4:2868–2880.Google Scholar
  54. 54.
    Danen EH, vanMuijen GN, Ruiter DJ. Role of integrins as signal transducing cell adhesion molecules in human cutaneous melanoma. Cancer Surv 1995; 24:43–65.PubMedGoogle Scholar
  55. 55.
    Liapis H, Flath A Kitazawa S. Integrin avb3 expression by bone-residing breast cancer metastases. Diagn Mol Pathol 1996; 5:127–135.PubMedCrossRefGoogle Scholar
  56. 56.
    Humphries MJ, Olden K, Yamada KM. A synthetic peptide from fibronectin inhibits experimental metastasis of murine melanoma cells. Science 1986; 233:467–470.PubMedCrossRefGoogle Scholar
  57. 57.
    Nakai M, Mundy GR, Williams PJ, Boyce B, Yoneda TA. A synthetic antagonist to laminin inhibits the formation of osteolytic metastases by human melanoma cells in nude mice. Cancer Res 1992; 52:5395–5399.PubMedGoogle Scholar
  58. 58.
    Matsuura N, Puzon-McLaughlin W, Irie A, Morikawa Y, Kakudo K, Takada Y. Induction of experimental bone metastasis in mice by transfection of integrin α4B1 into tumor cells. Am J Pathol 1996; 148:55–61.PubMedGoogle Scholar
  59. 59.
    Sung JV, Stubbs JT, Fisher L, Aaron AD, Thompson EW. Bone sialoprotein supports breast cancer cell adhesion proliferationand migration through differential usage of the alpha(v)-beta3 and alpha(v)-beta5 integrins. J Cell Physiol 1998; 176:482–494.PubMedCrossRefGoogle Scholar
  60. 60.
    Jacob K, Webber M, Benayahu D, Kleinman HK. Osteonectin promotes prostate cancer cell migration and invasion: a possible mechanism for metastasis to bone. Cancer Res 1999; 59:4453–4457.PubMedGoogle Scholar
  61. 61.
    Kostenuik PJ, Singh G, Orr FW. Transforming growth factor beta upregulates the integrin-mediated adhesion of human prostatic carcinoma cells to type I collagen. Clin Exp Metastasis 1997; 15:41–52.PubMedCrossRefGoogle Scholar
  62. 62.
    Liotta LA. Tumor invasion and metastasis-role of the extracellular matrix. Cancer Res 1986; 46:1–7.PubMedCrossRefGoogle Scholar
  63. 63.
    Curran S, Murray G. Matrix metalloproteinases in tumour invasion and metastasis. J Pathol 1999; 189:300–308.PubMedCrossRefGoogle Scholar
  64. 64.
    DeClerck YA, Shimada H, Taylor SM, Langley KE. Matrix metalloproteinases and their inhibitors in tumor progression. Ann NY Acad Sci 1994; 732:222–229.CrossRefGoogle Scholar
  65. 65.
    Masumori N, Tsukamoto T. Inhibitory effect of minocyclineon in vitro invasion and experimental metastasis of mouse renal adenocarcinoma. J Urology 1994; 151:1400–1404.Google Scholar
  66. 66.
    Davies B, Brown PD, East N, Crimmin MJ, Balkwill FR. A synthetic matrix metalloproteinase inhibitor decreases tumor burden and prolongs survival of mice bearing human ovarian carcinoma xenografts. Cancer Res 1993; 53:2087–2091.PubMedGoogle Scholar
  67. 67.
    Wang X, Fu X, Brown PD, Crimmin MJ, Hoffman RM. Matrix metalloproteinase inhibitor BB-94 (batimastat) inhibits human colon tumor growth and spread in a patient-like orthotopic model in nude mice. Cancer Res 1994; 54:4726–4728.PubMedGoogle Scholar
  68. 68.
    Zang YH, Heulsmann A, Tondravis MM, Mukherjee A, Abu-Amer Y. Tumor necrosis factor-α (TNF) stimulates RANKL-induced osteoclastogenesis via coupling of TNF type 1 receptor and RANK signaling pathways. J Biol Chem 2001; 276:563–568.CrossRefGoogle Scholar
  69. 69.
    Gearing AJ, Beckett P, Christodouiou M, et al. Processing of tumour necrosis factor-a by metalloproteinases. Nature 1994; 370:555–557.PubMedCrossRefGoogle Scholar
  70. 70.
    McGeehan GM, Becherer JD, Bast RC, et al. Regulation of tumour necrosis factor-a by a metalloproteinases inhibitor. Nature 1994; 370:558–561.PubMedCrossRefGoogle Scholar
  71. 71.
    Mann EA, Hibbs MS, Spiro JD, et al. Cytokine regulation of gelatinase production by head and neck squamous cell carcinoma: the role of tumor necrosis factor-alpha. Ann Otol Rhinol Laryngol 1995; 104:203–209.PubMedGoogle Scholar
  72. 72.
    Stetler-Stevenson MG, Krutzsch HC, Liotta. Tissue inhibitor of metalloproteinase (TIMP-2): a new member of the metalloproteinase inhibitor family. J Biol Chem 1989; 264:17,374–17,378.PubMedGoogle Scholar
  73. 73.
    Murphy G, Willenbrock F, Crabbe T, et al. Regulation of matrix metalloproteinase activity. Ann NY Acad Sci 1994; 732:31–41.PubMedCrossRefGoogle Scholar
  74. 74.
    DeClerck YA, Perez N, Shimada H, Boone TC, Langley KE, Taylor SM. Inhibition of invasion and metastasis in cells transfected with an inhibitor of metalloproteinases. Cancer Res 1992; 52:701–708.PubMedGoogle Scholar
  75. 75.
    Yoneda T, Sasaki A, Bunstan C, et al. Inhibition of osteolytic bone metastasis of breast cancer by combined treatment with the bisphosphonate ibandronate and tissue inhibitor of the matrix metalloproteinase-2. J Clin Invest 1997; 99:2509–2517.PubMedCrossRefGoogle Scholar
  76. 76.
    Basset P, Bellocq JP, Wolf C, et al. A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas. Nature 1990; 348:699–704.PubMedCrossRefGoogle Scholar
  77. 77.
    Basset P, Wolf C, Rouyer N, Bellocq JP, Rio MC, Chambon P. Stromelysin-3 in stromal tissue as a control factor in breast cancer behavior. Cancer 1994; 74:1045–1049.PubMedCrossRefGoogle Scholar
  78. 78.
    Manishen WJ, Sivananthan K, Orr FW. Resorbing bone stimulates tumor cell growth: a role for the host microenvironment in bone metastasis. Am J Pathol 1986; 123:39–45.PubMedGoogle Scholar
  79. 79.
    Reddy KB, Mangold GL, Tandon AK, et al. Inhibition of breast cancer cell growth in vitro by a tyrosine kinase inhibitor. Cancer Res 1992; 52:3636–3641.PubMedGoogle Scholar
  80. 80.
    Koutsilieris M, Frenette G, Lazure C, Lehoux JG, Govindan MV, Poychronakos C. Urokinase-type plasminogen activator: a paracrine factor regulating the bioavailability of IGFs in PA-III cell-induced osteoblastic metastases. Anticancer Res 1993; 13:481–486.PubMedGoogle Scholar
  81. 81.
    Rosol TJ, Capen CC, Horst RL. Effects of infusion of human parathyroid hormone-related protein-(1-40) in nude mice: histomorphometric and biochemical investigations. J Bone Miner Res 1988; 3:699–706.PubMedCrossRefGoogle Scholar
  82. 82.
    Guise TA, Yin JJ, Taylorn SD, et al. Evidence for a causal role of parathyroid hormone-related protein in the pathogenesis of human breast cancer-mediated osteolysis. J Clin Invest 1996; 98:1544–1549.PubMedCrossRefGoogle Scholar
  83. 83.
    Udagawa N, Takahashi N, Akatsu T, et al. The bone marrow-derived stromal cell lines MC3T3-G2/PA6 and ST2 support osteoclast-like cell differentiation in co-cultures with mouse spleen cells. Endocinology 125:1805–1813.Google Scholar
  84. 84.
    Jilka RL, Hamilton JW. Evidence for two pathways for stimulation of collagenolysis in bone. Calcif Tissue Int 1985; 37:300–306.PubMedCrossRefGoogle Scholar
  85. 85.
    Hicks DG, Gokan T, O’Keefe RJ, et al. Primary lymphoma of bone. Correlation of magnetic resonance imaging features with cytokine production by tumor cells. Cancer 1995; 75:973–980.PubMedCrossRefGoogle Scholar
  86. 86.
    O’Keefe RJ, Teot LA, Singh D, Puzas JE, Rosier RN, Hicks DG. Osteoclasts constitutively express regulators of bone resorption: an immunohistochemical and in situ hybridization study Lab. Invest. 1997; 76:457–465.Google Scholar
  87. 87.
    Zhang Y, Fujita N, Oh-hara T, Morinaga Y, Nakagawa T, Yamada M Tsuruo T. Production of interleukin-11 in bone-derived endothelial cells and its role in the formation of osteolyti bone metastasis. Oncogene 1998; 16:693–703.PubMedCrossRefGoogle Scholar
  88. 88.
    Thomson BM, Mundy GR, Chambers TJ. Tumor necrosis factor alpha and beta induce osteoblastic cells to stimulate osteoclastic bone resorption. J Immunol 1987; 138:775–779.PubMedGoogle Scholar
  89. 89.
    Suva LJ, Winslow GA, Wettenhall RE, et al. A parathyroid hormone-related protein implicated in malignant hypercalcemia: cloning and expression. Science 1987; 237:893–896.PubMedCrossRefGoogle Scholar
  90. 90.
    Bundred NJ, Walker RA, Ratcliffe WA, Warwich J, Morrison JM, Ratcliffe JG. Parathyroid hormone related protein and skeletal morbidity in breast cancer. Eur J Cancer 1992; 28:690–692.PubMedCrossRefGoogle Scholar
  91. 91.
    Abou-Samra A, Juppner H, Force T, et al. Expression cloning of a common receptor for parathyroid hormone and parathyroid hormone-related peptide from rat osteoblast-like cells: a single receptor stimulates intrcellular accumulation of both cAMP and inositol triphosphates and increases intracellular free calcium. Proc Natl Acad Sci USA 1992; 89:2732–2736.PubMedCrossRefGoogle Scholar
  92. 92.
    Southby J, Kissin MW, Danks JA, et al. Immunhistochemical localization of parathyroid hormone-related protein in breast cancer. Cancer Res 1990; 50:7710–7716.PubMedGoogle Scholar
  93. 93.
    Powell GJ, Southby J, Danks JA, et al. Localization of parathyroid hormone-related protein in breast cancer metastasis: increased incidence in bone compared with other sites. Cancer Res 1991; 51:3059–3061.PubMedGoogle Scholar
  94. 94.
    Bundred NJ, Ratcliffe WA, Walker RA, Coley S, Morrison JM, Ratcliffe JG. Parathyroid hormone related protein and hypercalcaemia in breast cancer. Br Med J 1991; 303:1506–1509.CrossRefGoogle Scholar
  95. 95.
    Guise TA. Parathyroid hormone-related protein and bone metastases. Cancer 1997; 80:1572–1580.PubMedCrossRefGoogle Scholar
  96. 96.
    Yin JJ, Selander K, Chirgwin JM, et al. TGF-beta signaling blackade inhibits PTHrP secretion by breast cancer cells and bone metastases development. J Clin Invest 1999; 103:197–206.PubMedCrossRefGoogle Scholar
  97. 97.
    Clarke NW, McClure J, George NJ. Morphometric evidence for bone resorption and replacement in prostate cancer. Br J Urol 1991; 68:74–80.PubMedGoogle Scholar
  98. 98.
    Urwin GH, Percival RC, Harris S, Beneton MN, Williams JL, Kanis JA. Generalised increase in bone resorption in carcinoma of the prostate. Br J Urol 1985; 57:721–723.PubMedGoogle Scholar
  99. 99.
    Garnero P. Markers of bone turnover in prostate cancer. Cancer Treat Rev 2001; 27:187–196.PubMedCrossRefGoogle Scholar
  100. 100.
    Revilla M, Arribas I, Sanchez-Chapado M, Villa LF, Bethencourt F, Rico H. Total and regional bone mass and biochemical markers of bone remodeling in metastatic prostate cancer. Prostate. 1998; 35:243–247.PubMedCrossRefGoogle Scholar
  101. 101.
    Iwamura M, Deftos LJ, Schoen S, Cocket ATK, Abrahamsson PA. Immunoreactive PTHrP is present in human seminal plasma and is of prostate origin. J Androl 1994; 15:410–414.PubMedGoogle Scholar
  102. 102.
    Iwamura M, Abrahamsson PA, Benning CM, Moynes RA, Gerhagen S, Cocket AT. Immunohistochemical localization of parathyroid hormone-related protein in prostatic intraepithelial neoplasia. Hum Pathol 1995; 26:797–801.PubMedCrossRefGoogle Scholar
  103. 103.
    Rabanni SA, Gladu J, Harakidas P, Jamison B, Goltzman D. Overproduction of parathyroid hormone-related peptide results in increased osteolytic skeletal metastasis by prostate cancer cells in vivo. Int J Cancer 1999; 18:257–264.Google Scholar
  104. 104.
    Deftos LJ. Prostate carcinoma: production of bioactive factors. Cancer 2000; 88:3002–3008.PubMedCrossRefGoogle Scholar
  105. 105.
    Dougherty KM, Blomme EA, Koh AJ, et al. Parathyroid hormonerelated protein as a growth regulator of prostate carcinoma. Cancer Res 1999; 59:6015–6022.PubMedGoogle Scholar
  106. 106.
    Blommme EAG, Dougherty KM, Pienta KJ, Capen CC, Rosol TJ, McCauley LK. Skeletal metastasis of prostate adenocarcinoma in rats: morphometeric analysis and role of parathyroid hormone-related protein. Prostate 1999; 39:187–197.CrossRefGoogle Scholar
  107. 107.
    Iddon J, Bundred NJ, Hoyland J, et al. Expression of parathyroid hormone-related protein and its receptor in bone metastases from prostate cancer. J Pathol 2000; 191:170–174.PubMedCrossRefGoogle Scholar
  108. 108.
    Zhang J, Dai J, Qi Y, et al. Osteoprotegerin inhibits prostate cancer-induced osteoclastogenesis and prevents prostate tumor growth in the bone. J Clin Invest 2001; 107:1235–1244.PubMedCrossRefGoogle Scholar
  109. 109.
    Brown JM, Corey E, Lee ZD, et al. Osteoprotegerin and RANK ligand expression in prostate cancer. Urology 2001; 57:611–616.PubMedCrossRefGoogle Scholar
  110. 110.
    Fata JE, Kong YY, Li J, et al. The osteoclast differentiation factor osteoprotegerin-ligand is essential for mammary gland development. Cell 2000; 103:41–59.PubMedCrossRefGoogle Scholar
  111. 111.
    Paterson AH. The potential role of bisphosphonates as adjuvant therapy in the prevention of bone metastases. Cancer 2000; 88:3038–3046.PubMedCrossRefGoogle Scholar
  112. 112.
    Smith R, Jiping W, Bryant J, et al. Primary breast cancer as a risk factor for bone recurrence: NSABP experience. Proc Am Soc Clin Oncol 1999; 18:457A.Google Scholar
  113. 113.
    Campbell FC, Blamey RW, Elston CW, Nicholson RI, Griffiths K, Haybittle JL. Oestrogen-receptor status and sites of metastasis in breast cancer. Br J Cancer 1981; 44:456–459.PubMedGoogle Scholar
  114. 114.
    Budd GT. Estrogen receptor profile of patients with breast cancer metastatic to bone marrow. J Surg Oncol 1983; 24:167–169.PubMedCrossRefGoogle Scholar
  115. 115.
    Kamby C, Rasmussen BB, Kristensen B. Oestrogen receptor status of primary breast carcinomas and their metastases: relation to pattern of spread and survival after recurrence. Br J Cancer 1989; 60:252–257.PubMedGoogle Scholar
  116. 116.
    Coleman RE, Rubens RD. Clinical course and prognostic factors following bone recurrence from breast cancer. Br J Cancer 1998; 77:336–340.PubMedGoogle Scholar

Copyright information

© Humana Press, Inc., Totowa, NJ 2006

Authors and Affiliations

  • David G. Hicks
    • 1
  1. 1.Department of Anatomic PathologyThe Cleveland Clinic FoundationCleveland

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