Table of Contents Author Guidelines Submit a Manuscript
Sarcoma
Volume 2011 (2011), Article ID 932451, 8 pages
http://dx.doi.org/10.1155/2011/932451
Review Article

The Bone Niche of Chondrosarcoma: A Sanctuary for Drug Resistance, Tumour Growth and also a Source of New Therapeutic Targets

1INSERM, UMR 957, Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculté de Médecine, 1 rue Gaston Veil, 44035 Nantes Cedex 1, 44035 Nantes, France
2Université de Nantes, Nantes Atlantique Universités, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, 44035 Nantes, France
3University Hospital, Hôtel Dieu, CHU de Nantes, 44035 Nantes, France
4EA3855, University Hospital, 2 bd Tonnelle, 37044 Tours Cedex, France
5University Hospital, Hôpital Trousseau, CHRU de Tours, 37042 Tours Cedex, France

Received 25 November 2010; Revised 28 January 2011; Accepted 10 February 2011

Academic Editor: Ole Nielsen

Copyright © 2011 E. David et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. S. Boeuf, P. Kunz, T. Hennig et al., “A chondrogenic gene expression signature in mesenchymal stem cells is a classifier of conventional central chondrosarcoma,” Journal of Pathology, vol. 216, no. 2, pp. 158–166, 2008. View at Publisher · View at Google Scholar · View at Scopus
  2. J. V. M. G. Bovée, A. M. Cleton-Jansen, A. H. M. Taminiau, and P. C. W. Hogendoorn, “Emerging pathways in the development of chondrosarcoma of bone and implications for targeted treatment,” Lancet Oncology, vol. 6, no. 8, pp. 599–607, 2005. View at Publisher · View at Google Scholar · View at Scopus
  3. T. Aigner, “Towards a new understanding and classification of chondrogenic neoplasias of the skeleton—biochemistry and cell biology of chondrosarcoma and its variants,” Virchows Archiv, vol. 441, no. 3, pp. 219–230, 2002. View at Publisher · View at Google Scholar · View at Scopus
  4. H. Gelderblom, P. C. W. Hogendoorn, S. D. Dijkstra et al., “The clinical approach towards chondrosarcoma,” Oncologist, vol. 13, no. 3, pp. 320–329, 2008. View at Publisher · View at Google Scholar · View at Scopus
  5. G. De Pinieux and C. Bouvier, “Recent advances in the biology of bone tumors and new diagnostic tools,” in Bone Cancer, D. Heymann, Ed., chapter 19, pp. 225–234, Academic Press, New York, NY, USA, 2010. View at Google Scholar
  6. Y. Wittrant, S. Théoleyre, C. Chipoy et al., “RANKL/RANK/OPG: new therapeutic targets in bone tumours and associated osteolysis,” Biochimica et Biophysica Acta, vol. 1704, no. 2, pp. 49–57, 2004. View at Publisher · View at Google Scholar · View at Scopus
  7. M. B. Meads, L. A. Hazlehurst, and W. S. Dalton, “The bone marrow microenvironment as a tumor sanctuary and contributor to drug resistance,” Clinical Cancer Research, vol. 14, no. 9, pp. 2519–2526, 2008. View at Publisher · View at Google Scholar · View at Scopus
  8. M. Campanacci, Bone and Soft Tissue Tumors, Springer, New York, NY, USA, 2nd edition, 1999.
  9. F. Y. Lee, H. J. Mankin, G. Fondren et al., “Chondrosarcoma of bone: an assessment of outcome,” Journal of Bone and Joint Surgery. Series A, vol. 81, no. 3, pp. 326–338, 1999. View at Google Scholar · View at Scopus
  10. E.L. Staals, E. Palmerini, S. Ferrari, and M. Mercuri, “Non-surgical treatment of chondrosarcoma: current concepts and future perspectives,” in Bone Cancer, D. Heymann, Ed., chapter 31, pp. 375–383, Academic Press, New York, NY, USA, 2010. View at Google Scholar
  11. J. Zhang, C. Niu, L. Ye et al., “Identification of the haematopoietic stem cell niche and control of the niche size,” Nature, vol. 425, no. 6960, pp. 836–841, 2003. View at Publisher · View at Google Scholar · View at Scopus
  12. L. M. Calvi, G. B. Adams, K. W. Weibrecht et al., “Osteoblastic cells regulate the haematopoietic stem cell niche,” Nature, vol. 425, no. 6960, pp. 841–846, 2003. View at Publisher · View at Google Scholar · View at Scopus
  13. F. Arai, A. Hirao, M. Ohmura et al., “Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche,” Cell, vol. 118, no. 2, pp. 149–161, 2004. View at Publisher · View at Google Scholar · View at Scopus
  14. S. K. Nilsson, H. M. Johnston, and J. A. Coverdale, “Spatial localization of transplanted hemopoietic stem cells: inferences for the localization of stem cell niches,” Blood, vol. 97, no. 8, pp. 2293–2299, 2001. View at Publisher · View at Google Scholar · View at Scopus
  15. H. Iwasaki and T. Suda, “Cancer stem cells and their niche,” Cancer Science, vol. 100, no. 7, pp. 1166–1172, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. G. W. Basak, A. S. Srivastava, R. Malhotra, and E. Carrier, “Multiple myeloma bone marrow niche,” Current Pharmaceutical Biotechnology, vol. 10, no. 3, pp. 335–346, 2009. View at Publisher · View at Google Scholar · View at Scopus
  17. S. W. Lane, D. T. Scadden, and D. G. Gilliland, “The leukemic stem cell niche: current concepts and therapeutic opportunities,” Blood, vol. 114, no. 6, pp. 1150–1157, 2009. View at Publisher · View at Google Scholar · View at Scopus
  18. T. L. Andersen, T. E. Sondergaard, K. E. Skorzynska et al., “A physical mechanism for coupling bone resorption and formation in adult human bone,” American Journal of Pathology, vol. 174, no. 1, pp. 239–247, 2009. View at Publisher · View at Google Scholar · View at Scopus
  19. M. K. Chang, L. J. Raggatt, K. A. Alexander et al., “Osteal tissue macrophages are intercalated throughout human and mouse bone lining tissues and regulate osteoblast function in vitro and in vivo,” Journal of Immunology, vol. 181, no. 2, pp. 1232–1244, 2008. View at Google Scholar · View at Scopus
  20. K. Ito, A. Hirao, F. Arai et al., “Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells,” Nature Medicine, vol. 12, no. 4, pp. 446–451, 2006. View at Publisher · View at Google Scholar
  21. K. Hosokawa, F. Arai, H. Yoshihara et al., “Function of oxidative stress in the regulation of hematopoietic stem cell-niche interaction,” Biochemical and Biophysical Research Communications, vol. 363, no. 3, pp. 578–583, 2007. View at Publisher · View at Google Scholar
  22. S. Paget, “The distribution of secondary growths in cancer of the breast,” The Lancet, vol. 133, no. 3421, pp. 571–573, 1889. View at Google Scholar · View at Scopus
  23. T. Yin and L. Li, “The stem cell niches in bone,” Journal of Clinical Investigation, vol. 116, no. 5, pp. 1195–1201, 2006. View at Publisher · View at Google Scholar · View at Scopus
  24. K. Hosokawa, F. Arai, H. Yoshihara et al., “Knockdown of N-cadherin suppresses the long-term engraftment of hematopoietic stem cells,” Blood, vol. 116, no. 4, pp. 554–563, 2010. View at Publisher · View at Google Scholar
  25. P. Clézardin, “Early bone metastasis-associated molecular and cellular events,” in Bone Cancer, D. Heymann, Ed., chapter 3, pp. 41–45, Academic Press, New York, NY, USA, 2010. View at Google Scholar
  26. C. Coghlin and G. I. Murray, “Current and emerging concepts in tumour metastasis,” Journal of Pathology, vol. 222, no. 1, pp. 1–15, 2010. View at Publisher · View at Google Scholar
  27. P. Perrot, J. Rousseau, A. -L. Bouffaut et al., “Safety concern between autologous fat graft, mesenchymal stem cell and osteosarcoma recurrence,” PLoS One, vol. 5, no. 6, Article ID e10999, 2010. View at Publisher · View at Google Scholar
  28. P. Picci, G. Sieberova, M. Alberghini et al., “Late sarcoma development after curettage and bone grafting of benign bone tumors,” European Journal of Radiology, vol. 77, no. 1, pp. 19–25, 2011. View at Publisher · View at Google Scholar
  29. R. Demicheli, M. W. Retsky, W. J. M. Hrushesky, and M. Baum, “Tumor dormancy and surgery-driven interruption of dormancy in breast cancer: learning from failures,” Nature Clinical Practice Oncology, vol. 4, no. 12, pp. 699–710, 2007. View at Publisher · View at Google Scholar · View at Scopus
  30. R. Demicheli, M. W. Retsky, W. J. M. Hrushesky, M. Baum, and I. D. Gukas, “The effects of surgery on tumor growth: a century of investigations,” Annals of Oncology, vol. 19, no. 11, pp. 1821–1828, 2008. View at Publisher · View at Google Scholar · View at Scopus
  31. E. Grimaud, C. Damiens, A. V. Rousselle, N. Passuti, D. Heymann, and F. Gouin, “Bone remodelling and tumour grade modifications induced by interactions between bone and Swarm rat chondrosarcoma,” Histology and Histopathology, vol. 17, no. 4, pp. 1103–1111, 2002. View at Google Scholar · View at Scopus
  32. M. Chanavaz, “The periosteum: the “umbilical cord” of bone. Quantification of the blood supply of cortical bone of periosteal origin,” Revue de Stomatologie et de Chirurgie Maxillo-Faciale, vol. 96, no. 4, pp. 262–267, 1995. View at Google Scholar · View at Scopus
  33. C. A. Squier, S. Ghoneim, and C. R. Kremenak, “Ultrastructure of the periosteum from membrane bone,” Journal of Anatomy, vol. 171, pp. 233–239, 1990. View at Google Scholar · View at Scopus
  34. X. Zhang, H. A. Awad, R. J. O'Keefe, R. E. Guldberg, and E. M. Schwarz, “A perspective: engineering periosteum for structural bone graft healing,” Clinical Orthopaedics and Related Research, vol. 466, no. 8, pp. 1777–1787, 2008. View at Publisher · View at Google Scholar · View at Scopus
  35. M. Söderström, T. Böhling, T. Ekfors, L. Nelimarkka, H. T. Aro, and E. Vuorio, “Molecular profiling of human chondrosarcomas for matrix production and cancer markers,” International Journal of Cancer, vol. 100, no. 2, pp. 144–151, 2002. View at Publisher · View at Google Scholar · View at Scopus
  36. S. Boeuf, P. Kunz, T. Hennig et al., “A chondrogenic gene expression signature in mesenchymal stem cells is a classifier of conventional central chondrosarcoma,” Journal of Pathology, vol. 216, no. 2, pp. 158–166, 2008. View at Publisher · View at Google Scholar · View at Scopus
  37. J. Diaz-Romero, S. Romeo, J. V. M. G. Bovée, P. C. W. Hogendoorn, P. F. Heini, and P. Mainil-Varlet, “Hierarchical clustering of flow cytometry data for the study of conventional central chondrosarcoma,” Journal of Cellular Physiology, vol. 225, no. 2, pp. 601–611, 2010. View at Publisher · View at Google Scholar
  38. F. Fiorenza, A. Abudu, R. J. Grimer et al., “Risk factors for survival and local control in chondrosarcoma of bone,” Journal of Bone and Joint Surgery. Series B, vol. 84, no. 1, pp. 93–99, 2002. View at Google Scholar · View at Scopus
  39. F. Y. Lee, H. J. Mankin, G. Fondren et al., “Chondrosarcoma of bone: An assessment of outcome,” Journal of Bone and Joint Surgery. Series A, vol. 81, no. 3, pp. 326–338, 1999. View at Google Scholar · View at Scopus
  40. S. Gitelis, F. Bertoni, P. Picci, and M. Campanacci, “Chondrosarcoma of bone. The experience at the Istituto Ortopedico Rizzoli,” Journal of Bone and Joint Surgery. Series A, vol. 63, no. 8, pp. 1248–1257, 1981. View at Google Scholar · View at Scopus
  41. T. Kalinski, S. Sel, I. Kouznetsova, M. Röpke, and A. Roessner, “Heterogeneity of angiogenesis and blood vessel maturation in cartilage tumors,” Pathology Research and Practice, vol. 205, no. 5, pp. 339–345, 2009. View at Publisher · View at Google Scholar · View at Scopus
  42. T. Kubo, T. Sugita, S. Shimose, T. Matsuo, K. Arihiro, and M. Ochi, “Expression of hypoxia-inducible factor-1α and its relationship to tumour angiogenesis and cell proliferation in cartilage tumours,” Journal of Bone and Joint Surgery. Series B, vol. 90, no. 3, pp. 364–370, 2008. View at Publisher · View at Google Scholar · View at Scopus
  43. C. Lin, R. McGough, B. Aswad, J. A. Block, and R. Terek, “Hypoxia induces HIF-1α and VEGF expression in chondrosarcoma cells and chondrocytes,” Journal of Orthopaedic Research, vol. 22, no. 6, pp. 1175–1181, 2004. View at Publisher · View at Google Scholar · View at Scopus
  44. G. Ayala, C. Liu, R. Nicosia, S. Horowitz, and R. Lackman, “Microvasculature and VEGF expression in cartilaginous tumors,” Human Pathology, vol. 31, no. 3, pp. 341–346, 2000. View at Google Scholar · View at Scopus
  45. R. L. McGough, C. Lin, P. Meitner, B. I. Aswad, and R. M. Terek, “Angiogenic cytokines in cartilage tumors,” Clinical Orthopaedics and Related Research, no. 397, pp. 62–69, 2002. View at Google Scholar · View at Scopus
  46. T. Furumatsu, K. Nishida, A. Kawai, M. Namba, H. Inoue, and Y. Ninomiya, “Human chondrosarcoma secretes vascular endothelial growth factor to induce tumor angiogenesis and stores basic fibroblast growth factor for regulation of its own growth,” International Journal of Cancer, vol. 97, no. 3, pp. 313–322, 2002. View at Publisher · View at Google Scholar · View at Scopus
  47. S. A. Nakagawa, A. Lopes, A. L. De Carvalho et al., “Nitric oxide synthases, cyclooxygenase-2, nitrotyrosine, and angiogenesis in chondrosarcoma and their relation to prognosis,” Journal of Bone and Joint Surgery. Series A, vol. 92, no. 8, pp. 1738–1746, 2010. View at Publisher · View at Google Scholar
  48. S. Boeuf, J. V. M. G. Bovée, B. Lehner, P. C. W. Hogendoorn, and W. Richter, “Correlation of hypoxic signalling to histological grade and outcome in cartilage tumours,” Histopathology, vol. 56, no. 5, pp. 641–651, 2010. View at Publisher · View at Google Scholar · View at Scopus
  49. T. Schioppa, B. Uranchimeg, A. Saccani et al., “Regulation of the chemokine receptor CXCR4 by hypoxia,” Journal of Experimental Medicine, vol. 198, no. 9, pp. 1391–1402, 2003. View at Publisher · View at Google Scholar · View at Scopus
  50. J. Wang, J. Wang, Y. Sun et al., “Diverse signaling pathways through the SDF-1/CXCR4 chemokine axis in prostate cancer cell lines leads to altered patterns of cytokine secretion and angiogenesis,” Cellular Signalling, vol. 17, no. 12, pp. 1578–1592, 2005. View at Publisher · View at Google Scholar · View at Scopus
  51. R. N. Kaplan, R. D. Riba, S. Zacharoulis et al., “VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche,” Nature, vol. 438, no. 7069, pp. 820–827, 2005. View at Publisher · View at Google Scholar · View at Scopus
  52. X. Sun, L. Wei, Q. Chen, and R. M. Terek, “CXCR4/SDF1 mediate hypoxia induced chondrosarcoma cell invasion through ERK signaling and increased MMP1 expression,” Molecular Cancer, vol. 9, article no. 17, 2010. View at Publisher · View at Google Scholar · View at Scopus
  53. T. H. Lai, Y. C. Fong, W. M. Fu, R. S. Yang, and C. H. Tang, “Stromal cell-derived factor-1 increase αvβ3 integrin expression and invasion in human chondrosarcoma cells,” Journal of Cellular Physiology, vol. 218, no. 2, pp. 334–342, 2009. View at Publisher · View at Google Scholar · View at Scopus
  54. C. H. Tang, A. Yamamoto, Y. T. Lin, YI. C. Fong, and T. W. Tan, “Involvement of matrix metalloproteinase-3 in CCL5/CCR5 pathway of chondrosarcomas metastasis,” Biochemical Pharmacology, vol. 79, no. 2, pp. 209–217, 2010. View at Publisher · View at Google Scholar · View at Scopus
  55. S. Stier, Y. Ko, R. Forkert et al., “Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size,” Journal of Experimental Medicine, vol. 201, no. 11, pp. 1781–1791, 2005. View at Publisher · View at Google Scholar · View at Scopus
  56. J. C. Reichert, V. M. C. Quent, L. J. Burke, S. H. Stansfield, J. A. Clements, and D. W. Hutmacher, “Mineralized human primary osteoblast matrices as a model system to analyse interactions of prostate cancer cells with the bone microenvironment,” Biomaterials, vol. 31, no. 31, pp. 7928–7936, 2010. View at Publisher · View at Google Scholar
  57. Y. J. Chen, Y. Y. Wei, H. T. Chen et al., “Osteopontin increases migration and MMP-9 up-regulation via αvβ3 integrin, FAK, ERK, and NF-κB-dependent pathway in human chondrosarcoma cells,” Journal of Cellular Physiology, vol. 221, no. 1, pp. 98–108, 2009. View at Publisher · View at Google Scholar · View at Scopus
  58. J. B. Vincourt, S. Etienne, J. Cottet et al., “C-propeptides of procollagens Iα1 and II that differentially accumulate in enchondromas versus chondrosarcomas regulate tumor cell survival and migration,” Cancer Research, vol. 70, no. 11, pp. 4739–4748, 2010. View at Publisher · View at Google Scholar · View at Scopus
  59. T. Furumatsu, N. Yamaguchi, K. Nishida et al., “Endostatin inhibits adhesion of endothelial cells to collagen I via αβ integrin, a possible cause of prevention of chondrosarcoma growth,” Journal of Biochemistry, vol. 131, no. 4, pp. 619–626, 2002. View at Google Scholar · View at Scopus
  60. P. Rutkowski, J. Kamińska, M. Kowalska, W. Ruka, and J. Steffen, “Cytokine and cytokine receptor serum levels in adult bone sarcoma patients: correlations with local tumor extent and prognosis,” Journal of Surgical Oncology, vol. 84, no. 3, pp. 151–159, 2003. View at Publisher · View at Google Scholar · View at Scopus
  61. T. Kalinski, S. Krueger, S. Sel, K. Werner, M. Röpke, and A. Roessner, “ADAMTS1 is regulated by interleukin-1β, not by hypoxia, in chondrosarcoma,” Human Pathology, vol. 38, no. 1, pp. 86–94, 2007. View at Publisher · View at Google Scholar · View at Scopus
  62. E. KerkelÄ, T. Böhling, R. Herva, J. A. Uria, and U. Saarialho-Kere, “Human macrophage metalloelastase (MMP-12) expression is induced in chondrocytes during fetal development and malignant transformation,” Bone, vol. 29, no. 5, pp. 487–493, 2001. View at Publisher · View at Google Scholar · View at Scopus
  63. S. W. Yoon, J. S. Chun, M. H. Sung, J. Y. Kim, and H. Poo, “α-MSH inhibits TNF-α-induced matrix metalloproteinase-13 expression by modulating p38 kinase and nuclear factor κB signaling in human chondrosarcoma HTB-94 cells,” Osteoarthritis and Cartilage, vol. 16, no. 1, pp. 115–124, 2008. View at Publisher · View at Google Scholar
  64. Y. Y. Yeh, C. C. Chiao, W. Y. Kuo et al., “TGF-β1 increases motility and αvβ3 integrin up-regulation via PI3K, Akt and NF-κB-dependent pathway in human chondrosarcoma cells,” Biochemical Pharmacology, vol. 75, no. 6, pp. 1292–1301, 2008. View at Publisher · View at Google Scholar · View at Scopus
  65. Y. C. Fong, T. M. Li, C. M. Wu et al., “BMP-2 increases migration of human chondrosarcoma cells via PI3K/Akt pathway,” Journal of Cellular Physiology, vol. 217, no. 3, pp. 846–855, 2008. View at Publisher · View at Google Scholar · View at Scopus
  66. E. David, P. Guihard, B. Brounais et al., “Direct anti-cancer effect of oncostatin M on chondrosarcoma,” International Journal of Cancer, vol. 128, no. 8, pp. 1822–1835, 2011. View at Publisher · View at Google Scholar
  67. J. A. Joyce and J. W. Pollard, “Microenvironmental regulation of metastasis,” Nature Reviews Cancer, vol. 9, no. 4, pp. 239–252, 2009. View at Publisher · View at Google Scholar · View at Scopus
  68. M. B. Meads, L. A. Hazlehurst, and W. S. Dalton, “The bone marrow microenvironment as a tumor sanctuary and contributor to drug resistance,” Clinical Cancer Research, vol. 14, no. 9, pp. 2519–2526, 2008. View at Publisher · View at Google Scholar · View at Scopus
  69. M. Konopleva, Y. Tabe, Z. Zeng, and M. Andreeff, “Therapeutic targeting of microenvironmental interactions in leukemia: mechanisms and approaches,” Drug Resistance Updates, vol. 12, no. 4-5, pp. 103–113, 2009. View at Publisher · View at Google Scholar · View at Scopus
  70. K. Scotlandi, P. Picci, and H. Kovar, “Targeted therapies in bone sarcomas,” Current Cancer Drug Targets, vol. 9, no. 7, pp. 843–853, 2009. View at Publisher · View at Google Scholar · View at Scopus
  71. H. Morioka, L. Weissbach, T. Vogel et al., “Antiangiogenesis treatment combined with chemotherapy produces chondrosarcoma necrosis,” Clinical Cancer Research, vol. 9, no. 3, pp. 1211–1217, 2003. View at Google Scholar · View at Scopus
  72. K. M. Sutton, M. Wright, G. Fondren, C. A. Towle, and H. J. Mankin, “Cyclooxygenase-2 expression in chondrosarcoma,” Oncology, vol. 66, no. 4, pp. 275–280, 2004. View at Publisher · View at Google Scholar · View at Scopus
  73. Y. M. Schrage, I. Machado, D. Meijer et al., “COX-2 expression in chondrosarcoma: a role for celecoxib treatment?” European Journal of Cancer, vol. 46, no. 3, pp. 616–624, 2010. View at Publisher · View at Google Scholar · View at Scopus
  74. X. Sun, L. Wei, Q. Chen, and R. M. Terek, “HDAC4 represses vascular endothelial growth factor expression in chondrosarcoma by modulating RUNX2 activity,” Journal of Biological Chemistry, vol. 284, no. 33, pp. 21881–21890, 2009. View at Publisher · View at Google Scholar · View at Scopus
  75. F. Blanchard and C. Chipoy, “Histone deacetylase inhibitors: new drugs for the treatment of inflammatory diseases?” Drug Discovery Today, vol. 10, no. 3, pp. 197–204, 2005. View at Publisher · View at Google Scholar · View at Scopus
  76. R. Sakimura, K. Tanaka, S. Yamamoto et al., “The effects of histone deacetylase inhibitors on the induction of differentiation in chondrosarcoma cells,” Clinical Cancer Research, vol. 13, no. 1, pp. 275–282, 2007. View at Publisher · View at Google Scholar · View at Scopus
  77. B. Ory, G. Moriceau, F. Redini, and D. Heymann, “mTOR inhibitors (Rapamycin and its derivatives) and nitrogen containing bisphosphonates: bi-functional compounds for the treatment of bone tumours,” Current Medicinal Chemistry, vol. 14, no. 13, pp. 1381–1387, 2007. View at Publisher · View at Google Scholar · View at Scopus
  78. D. Heymann, B. Ory, F. Gouin, J. R. Green, and F. Rédini, “Bisphosphonates: new therapeutic agents for the treatment of bone tumors,” Trends in Molecular Medicine, vol. 10, no. 7, pp. 337–343, 2004. View at Publisher · View at Google Scholar · View at Scopus
  79. R. E. Brown, “Brief communication: morphoproteomic portrait of the mTOR pathway in mesenchymal chondrosarcoma,” Annals of Clinical and Laboratory Science, vol. 34, no. 4, pp. 397–399, 2004. View at Google Scholar · View at Scopus
  80. G. Moriceau, B. Ory, L. Mitrofan et al., “Zoledronic acid potentiates mTOR inhibition and abolishes the resistance of osteosarcoma cells to RAD001 (everolimus): pivotal role of the prenylation process,” Cancer Research, vol. 70, no. 24, pp. 10329–10339, 2010. View at Publisher · View at Google Scholar
  81. O. Merimsky, R. Bernstein-Molho, and R. Sagi-Eisenberg, “Targeting the mammalian target of rapamycin in myxoid chondrosarcoma,” Anti-Cancer Drugs, vol. 19, no. 10, pp. 1019–1021, 2008. View at Publisher · View at Google Scholar · View at Scopus
  82. O. Kollet, A. Dar, S. Shivtiel et al., “Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells,” Nature Medicine, vol. 12, no. 6, pp. 657–664, 2006. View at Publisher · View at Google Scholar · View at Scopus
  83. T. J. Lai, S. F. Hsu, T. M. Li et al., “Alendronate inhibits cell invasion and MMP-2 secretion in human chondrosarcoma cell line,” Acta Pharmacologica Sinica, vol. 28, no. 8, pp. 1231–1235, 2007. View at Publisher · View at Google Scholar · View at Scopus
  84. T. Kubo, S. Shimose, T. Matsuo et al., “Inhibitory effects of a new bisphosphonate, minodronate, on proliferation and invasion of a variety of malignant bone tumor cells,” Journal of Orthopaedic Research, vol. 24, no. 6, pp. 1138–1144, 2006. View at Publisher · View at Google Scholar
  85. F. Gouin, B. Ory, F. Rédini, and D. Heymann, “Zoledronic acid slows down rat primary chondrosarcoma development, recurrent tumor progression after intralesional curretage and increases overall survival,” International Journal of Cancer, vol. 119, no. 5, pp. 980–984, 2006. View at Publisher · View at Google Scholar · View at Scopus