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Bone metabolism and new targets for intervention

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Abstract

Bone metastasis is a common complication of prostate cancer and is associated with significant morbidity for patients. Bone metabolism and prostate cancer metastasis to bone are complex processes. The interactions between host cells and metastatic prostate cancer cells are important components of organ-specific cancer progression. In addition to traditional treatment approaches, targeted therapy is currently becoming more popular. Bone metabolism, metastatic processes of prostate cancer, and the targeting of treatment for advanced disease are discussed here.

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References and Recommended Reading

  1. Rubin MA, Putzi M, Mucci N, et al.: Rapid (“warm”) autopsy study for procurement of metastatic prostate cancer. Clin Cancer Res 2000, 6:1038–1045.

    PubMed  CAS  Google Scholar 

  2. Oades GM, Coxon J, Colston KW: The potential role of bisphosphonates in prostate cancer. Prostate Cancer Prostatic Dis 2002, 5:264–272.

    Article  PubMed  CAS  Google Scholar 

  3. Paget S: The distribution of growths in cancer of the breast. Lancet 1889, i:571.

    Article  Google Scholar 

  4. Ewing J: A Treatise on Tumors. Philadelphia: WB Saunders; 1928.

    Google Scholar 

  5. Fidler IJ: The organ microenvironment and cancer metastasis. Differentiation 2002, 70:498–505.

    Article  PubMed  Google Scholar 

  6. Bubendorf L, Schopfer A, Wagner U, et al.: Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. Hum Pathol 2000, 31:578–583.

    Article  PubMed  CAS  Google Scholar 

  7. Kahn D, Weiner GJ, Ben-Haim S, et al.: Positron emission tomographic measurement of bone marrow blood flow to the pelvis and lumbar vertebrae in young normal adults. Blood 1994, 83:958–963.

    PubMed  CAS  Google Scholar 

  8. van der Pluijm G, Sijmons B, Vloedgraven H, et al.: Monitoring metastatic behavior of human tumor cells in mice with species-specific polymerase chain reaction: elevated expression of angiogenesis and bone resorption stimulators by breast cancer in bone metastases. J Bone Miner Res 2001, 16:1077–1091.

    Article  PubMed  Google Scholar 

  9. Hauschka PV, Mavrakos AE, Iafrati MD, et al.: Growth factors in bone matrix: isolation of multiple types by affinity chromatography on heparin-sepharose. J Biol Chem 1986, 261:12665–12674.

    PubMed  CAS  Google Scholar 

  10. Pfeilschifter J, Mundy GR: Modulation of type beta transforming growth factor activity in bone cultures by osteotropic homrones. Proc Natl Acad Sci U S A 1987, 84:2024–2028.

    Article  PubMed  CAS  Google Scholar 

  11. Roodman GD: Cell biology of the osteoclast. Exp Hematol 1999, 27:1229–1241.

    Article  PubMed  CAS  Google Scholar 

  12. Yasuda H, Shima N, Nakagawa N, et al.: Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci U S A 1998, 95:3597–3602.

    Article  PubMed  CAS  Google Scholar 

  13. 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.

    Article  PubMed  CAS  Google Scholar 

  14. Min H, Morony S, Sarosi I, et al.: Osteoprotegerin reverses osteoporosis by inhibiting endosteal osteoclasts and prevents vascular calcification by blocking a process resembling osteoclastogenesis. J Exp Med 2000, 192:463–474.

    Article  PubMed  CAS  Google Scholar 

  15. Mizuno A, Amizuka N, Irie K, et al.: Severe osteoporosis in mice lacking osteoclastogenesis inhibitory factor/osteoprotegerin. Biochem Biophys Res Commun 1998, 247:610–615.

    Article  PubMed  CAS  Google Scholar 

  16. Ducy P, Zhang R, Geoffroy V, et al.: Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 1997, 89:747–754.

    Article  PubMed  CAS  Google Scholar 

  17. Yang X, Karsenty G: Transcription factors in bone: developmental and pathological aspects. Trends Mol Med 2002, 8:340–345.

    Article  PubMed  CAS  Google Scholar 

  18. Nakashima K, Zhou X, Kunkel G, et al.: The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 2002, 108:17–29.

    Article  PubMed  CAS  Google Scholar 

  19. Lee KS, Kim HJ, Li QL, et al.: Runx2 is a common target of transforming growth factor beta1 and bone morphogenetic protein 2, and cooperation between Runx2 and Smad5 induces osteoblast-specific gene expression in the pluripotent mesenchymal precursor cell line C2C12. Mol Cell Biol 2000, 20:8783–8792.

    Article  PubMed  CAS  Google Scholar 

  20. Kim HJ, Kim JH, Bae SC, et al.: The protein kinase C pathway plays a central role in the fibroblast growth factor-stimulated expression and transactivation activity of Runx2. J Biol Chem 2003, 278:319–326. [Epub October 25, 2002]

    Article  PubMed  CAS  Google Scholar 

  21. Taichman RS, Cooper C, Keller ET, et al.: Use of the stromal cell-derived factor-1/CXCR4 pathway in prostate cancer metastasis to bone. Cancer Res 2002, 62:1832–1837.

    PubMed  CAS  Google Scholar 

  22. Sun YX, Schneider A, Jung Y, et al.: Skeletal localization and neutralization of the SDF-1(CXCL12)/CXCR4 axis blocks prostate cancer metastasis and growth in osseous sites in vivo. J Bone Miner Res 2005, 20:318–329.

    Article  PubMed  CAS  Google Scholar 

  23. Jacob K, Webber M, Benayahu D, et al.: Osteonectin promotes prostate cancer cell migration and invasion: a possible mechanism for metastasis to bone. Cancer Res 1999, 59:4453–4457.

    PubMed  CAS  Google Scholar 

  24. Hullinger TG, McCauley LK, DeJoode ML, et al.: Effect of bone proteins on human prostate cancer cell lines in vitro. Prostate 1998, 36:14–22.

    Article  PubMed  CAS  Google Scholar 

  25. Festuccia C, Bologna M, Gravina GL, et al.: Osteoblast conditioned media contain TGF-beta1 and modulate the migration of prostate tumor cells and their interactions with extracellular matrix components. Int J Cancer 1999, 81:395–403.

    Article  PubMed  CAS  Google Scholar 

  26. Autzen P, Robson CN, Bjartell A, et al.: Bone morphogenetic protein 6 in skeletal metastases from prostate cancer and other common human malignancies. Br J Cancer 1998, 78:1219–23.

    PubMed  CAS  Google Scholar 

  27. Harris SE, Harris MA, Mahy P, et al.: Expression of bone morphogenetic protein messenger RNAs by normal rat and human prostate and prostate cancer cells. Prostate 1994, 24:204–211.

    Article  PubMed  CAS  Google Scholar 

  28. Bentley H, Hamdy FC, Hart KA, et al.: Expression of bone morphogenetic proteins in human prostatic adenocarcinoma and benign prostatic hyperplasia. Br J Cancer 1992, 66:1159–1163.

    PubMed  CAS  Google Scholar 

  29. Ebisawa T, Tada K, Kitajima I, et al.: Characterization of bone morphogenetic protein-6 signaling pathways in osteoblast differentiation. J Cell Sci 1999, 112:3519–3527.

    PubMed  CAS  Google Scholar 

  30. Marquardt H, Lioubin MN, Ikeda T: Complete amino acid sequence of human transforming growth factor type beta 2. J Biol Chem 1987, 262:12127–12131.

    PubMed  CAS  Google Scholar 

  31. Shariat SF, Shalev M, Menesses-Diaz A, et al.: Preoperative plasma levels of transforming growth factor beta(1) (TGF-beta(1)) strongly predict progression in patients undergoing radical prostatectomy. J Clin Oncol 2001, 19:2856–2864.

    PubMed  CAS  Google Scholar 

  32. Chan JM, Stampfer MJ, Giovannucci E, et al.: Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science 1998, 279:563–566.

    Article  PubMed  CAS  Google Scholar 

  33. Baserga R: The insulin-like growth factor I receptor: a key to tumor growth? Cancer Res 1995, 55:249–252.

    PubMed  CAS  Google Scholar 

  34. Funa K, Eriksson B, Wilander E, et al.: In situ hybridization study of chromogranin A and B mRNA in carcinoid tumors. Histochemistry 1991, 95:555–559.

    Article  PubMed  CAS  Google Scholar 

  35. Fudge K, Wang CY, Stearns ME: Immunohistochemistry analysis of platelet-derived growth factor A and B chains and platelet-derived growth factor alpha and beta receptor expression in benign prostatic hyperplasias and Gleasongraded human prostate adenocarcinomas. Mod Pathol 1994, 7:549–554.

    PubMed  CAS  Google Scholar 

  36. Matuo Y, Nishi N, Matsui S, et al.: Heparin binding affinity of rat prostatic growth factor in normal and cancerous prostates: partial purification and characterization of rat prostatic growth factor in the Dunning tumor. Cancer Res 1987, 47:188–192.

    PubMed  CAS  Google Scholar 

  37. Ferrer FA, Miller LJ, Andrawis RI, et al.: Vascular endothelial growth factor (VEGF) expression in human prostate cancer: in situ and in vitro expression of VEGF by human prostate cancer cells. J Urol 1997, 157:2329–2333.

    Article  PubMed  CAS  Google Scholar 

  38. Kasperk CH, Borcsok I, Schairer HU, et al.: Endothelin-1 is a potent regulator of human bone cell metabolism in vitro. Calcif Tissue Int 1997, 60:368–374.

    Article  PubMed  CAS  Google Scholar 

  39. Nelson JB, Hedican SP, George DJ, et al.: Identification of endothelin-1 in the pathophysiology of metastatic adenocarcinoma of the prostate. Nat Med 1995, 1:944–949.

    Article  PubMed  CAS  Google Scholar 

  40. Guise TA, Yin JJ, Mohammad KS: Role of endothelin-1 in osteoblastic bone metastases. Cancer 2003, 97(3 Suppl):779–784.

    Article  PubMed  Google Scholar 

  41. Rabbani SA, Desjardins J, Bell AW, et al.: An aminoterminal fragment of urokinase isolated from a prostate cancer cell line (PC-3) is mitogenic for osteoblast-like cells. Biochem Biophys Res Commun 1990, 173:1058–1064.

    Article  PubMed  CAS  Google Scholar 

  42. Koutsilieris M: Osteoblastic metastasis in advanced prostate cancer. Anticancer Res 1993, 13:443–449.

    PubMed  CAS  Google Scholar 

  43. Achbarou A, Kaiser S, Tremblay G, et al.: Urokinase overproduction results in increased skeletal metastasis by prostate cancer cells in vivo. Cancer Res 1994, 54:2372–2377.

    PubMed  CAS  Google Scholar 

  44. Cramer SD, Chen Z, Peehl DM: Prostate specific antigen cleaves parathyroid hormone-related protein in the PTH-like domain: inactivation of PTHrP-stimulated cAMP accumulation in mouse osteoblasts. J Urol 1996, 156(2 Part 1):526–531.

    PubMed  CAS  Google Scholar 

  45. Stamenkovic I: Extracellular matrix remodelling: the role of matrix metalloproteinases. J Pathol 2003, 200:448–464.

    Article  PubMed  CAS  Google Scholar 

  46. Upadhyay J, Shekarriz B, Nemeth JA, et al.: Membrane type 1-matrix metalloproteinase (MT1-MMP) and MMP-2 immunolocalization in human prostate: change in cellular localization associated with high-grade prostatic intraepithelial neoplasia. Clin Cancer Res 1999, 5:4105–4110.

    PubMed  CAS  Google Scholar 

  47. Brown JM, Vessella RL, Kostenuik PJ, et al.: Serum osteoprotegerin levels are increased in patients with advanced prostate cancer. Clin Cancer Res 2001, 7:2977–2983.

    PubMed  CAS  Google Scholar 

  48. Roland SI: Calcium studies in ten cases of osteoblastic prostatic metastasis. J Urol 1958, 79:339–342.

    PubMed  CAS  Google Scholar 

  49. Garnero P, Buchs N, Zekri J, et al.: Markers of bone turnover for the management of patients with bone metastases from prostate cancer. Br J Cancer 2000, 82:858–864.

    Article  PubMed  CAS  Google Scholar 

  50. Sano M, Kushida K, Takahashi M, et al.: Urinary pyridino-line and deoxypyridinoline in prostate carcinoma patients with bone metastasis. Br J Cancer 1994, 70:701–703.

    PubMed  CAS  Google Scholar 

  51. Nielsen OS, Munro AJ, Tannock IF: Bone metastases: pathophysiology and management policy. J Clin Oncol 1991, 9:509–524.

    PubMed  CAS  Google Scholar 

  52. Yi B, Williams PJ, Niewolna M, et al.: Tumor-derived platelet-derived growth factor-BB plays a critical role in osteosclerotic bone metastasis in an animal model of human breast cancer. Cancer Res 2002, 62:917–923.

    PubMed  CAS  Google Scholar 

  53. Rogers MJ, Watts DJ, Russell RG: Overview of bisphosphonates. Cancer 1997, 80(8 Suppl):1652–1660.

    Article  PubMed  CAS  Google Scholar 

  54. Corey E, Brown LG, Quinn JE, et al.: Zoledronic acid exhibits inhibitory effects on osteoblastic and osteolytic metastases of prostate cancer. Clin Cancer Res 2003, 9:295–306.

    PubMed  CAS  Google Scholar 

  55. Lee YP, Schwarz EM, Davies M, et al.: Use of zoledronate to treat osteoblastic versus osteolytic lesions in a severecombined-immunodeficient mouse model. Cancer Res 2002, 62:5564–5570.

    PubMed  CAS  Google Scholar 

  56. Miwa S, Mizokami A, Keller ET, et al.: The bisphosphonate YM529 inhibits osteolytic and osteoblastic changes and CXCR-4-induced invasion in prostate cancer. Cancer Res 2005, 65:8818–8825.

    Article  PubMed  CAS  Google Scholar 

  57. Nelson J, Bagnato A, Battistini B, et al.: The endothelin axis: emerging role in cancer. Nat Rev Cancer 2003, 3:110–116.

    Article  PubMed  CAS  Google Scholar 

  58. Gohji K, Kitazawa S, Tamada H, et al.: Expression of endothelin receptor A associated with prostate cancer progression. J Urol 2001, 165:1033–1036.

    Article  PubMed  CAS  Google Scholar 

  59. Jimeno A, Carducci M: Atrasentan: targeting the endothelin axis in prostate cancer. Expert Opin Investig Drugs 2004, 13:1631–1640.

    Article  PubMed  CAS  Google Scholar 

  60. Carducci MA, Padley RJ, Breul J, et al.: Effect of endothelin-A receptor blockade with atrasentan on tumor progression in men with hormone-refractory prostate cancer: a randomized, phase II, placebo-controlled trial. J Clin Oncol 2003, 21:679–689.

    Article  PubMed  CAS  Google Scholar 

  61. Carducci MA, Nelson JB, Saad F, et al.: Effects of atrasentan on disease progression and biological markers in men with metastatic hormone-refractory prostate cancer: phase 3 study. J Clin Oncol 2004, 22:384s.

    Google Scholar 

  62. Kim SJ, Uehara H, Yazici S, et al.: Targeting platelet-derived growth factor receptor on endothelial cells of multidrug-resistant prostate cancer. J Natl Cancer Inst 2006, 98:783–793.

    Article  PubMed  CAS  Google Scholar 

  63. Tannock IF, de Wit R, Berry WR, et al.: Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 2004, 351:1502–1512.

    Article  PubMed  CAS  Google Scholar 

  64. Barnes S: Effect of genistein on in vitro and in vivo models of cancer. J Nutr 1995, 125(3 Suppl):777S–783S.

    PubMed  CAS  Google Scholar 

  65. Li Y, Kucuk O, Hussain M, et al.: Antitumor and anti-metastatic activaties of docetaxel are enhanced by genistein through regulation of osteoprotegerin/receptor activator of nuclear factor-kappaB (RANK)/RANK ligand/MMP-9 signaling in prostate cancer. Cancer Res 2006, 66:4816–4825.

    Article  PubMed  CAS  Google Scholar 

  66. Edlund M, Miyamoto T, Sikes RA, et al.: Integrin expression and usage by prostate cancer cell lines on laminin substrata. Cell Growth Differ 2001, 12:99–107.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Urology, School of Medicine, Zonguldak Karaelmas University, Zonguldak, 67600, Turkey

    Bulent Akduman MD

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  1. Bulent Akduman MD
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  2. E. David Crawford MD
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Correspondence to Bulent Akduman MD.

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Akduman, B., Crawford, E.D. Bone metabolism and new targets for intervention. Curr Urol Rep 8, 233–238 (2007). https://doi.org/10.1007/s11934-007-0011-y

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