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Sarcoma
Volume 2014, Article ID 261804, 9 pages
http://dx.doi.org/10.1155/2014/261804
Research Article

Aberrant Hedgehog Signaling and Clinical Outcome in Osteosarcoma

Winnie W. Lo,1,2 Dushanthi Pinnaduwage,2 Nalan Gokgoz,2 Jay S. Wunder,2,3,4 and Irene L. Andrulis1,2

1Department of Molecular Genetics, University of Toronto, ON, Canada M5S 1A8
2Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, Canada M5G 1X5
3University Musculoskeletal Oncology Unit, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5
4Department of Surgery, University of Toronto, ON, Canada M5G 1L5

Received 28 October 2013; Revised 5 February 2014; Accepted 17 February 2014; Published 30 March 2014

Academic Editor: Akira Kawai

Copyright © 2014 Winnie W. Lo 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. J. Levesque, R. Marx, R. S. Bell, J. S. Winder, R. A. Kandel, and L. M. White, A Clinical Guide to Primary Bone Tumors, Williams & Wilkins, Philadelphia, Pa, USA, 1998.
  2. M. P. Link, A. M. Goorin, and A. W. Miser, “The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity,” The New England Journal of Medicine, vol. 314, no. 25, pp. 1600–1606, 1986. View at Google Scholar · View at Scopus
  3. F. Eilber, A. Giuliano, and J. Eckhardt, “Adjuvant chemotherapy for osteosarcoma: a randomized prospective trial,” Journal of Clinical Oncology, vol. 5, no. 1, pp. 21–26, 1987. View at Google Scholar · View at Scopus
  4. S. S. Bielack, B. Kempf-Bielack, G. Delling et al., “Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols,” Journal of Clinical Oncology, vol. 20, no. 3, pp. 776–790, 2002. View at Publisher · View at Google Scholar · View at Scopus
  5. L. L. Rubin and F. J. de Sauvage, “Targeting the Hedgehog pathway in cancer,” Nature Reviews Drug Discovery, vol. 5, no. 12, pp. 1026–1033, 2006. View at Publisher · View at Google Scholar · View at Scopus
  6. J. Jiang and C. C. Hui, “Hedgehog signaling in development and cancer,” Developmental Cell, vol. 15, no. 6, pp. 801–812, 2008. View at Publisher · View at Google Scholar · View at Scopus
  7. D. M. Berman, S. S. Karhadkar, A. Maitra et al., “Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours,” Nature, vol. 425, no. 6960, pp. 846–851, 2003. View at Publisher · View at Google Scholar · View at Scopus
  8. C. Dierks, J. Grbic, K. Zirlik et al., “Essential role of stromally induced Hedgehog signaling in B-cell malignancies,” Nature Medicine, vol. 13, no. 8, pp. 944–951, 2007. View at Publisher · View at Google Scholar · View at Scopus
  9. G. V. Hegde, K. J. Peterson, K. Emanuel et al., “Hedgehog-induced survival of B-cell chronic lymphocytic leukemia cells in a stromal cell microenvironment: a potential new therapeutic target,” Molecular Cancer Research, vol. 6, no. 12, pp. 1928–1936, 2008. View at Publisher · View at Google Scholar · View at Scopus
  10. S. S. Karhadkar, G. S. Bova, N. Abdallah et al., “Hedgehog signalling in prostate regeneration, neoplasia and metastasis,” Nature, vol. 431, no. 7009, pp. 707–712, 2004. View at Publisher · View at Google Scholar · View at Scopus
  11. S. P. Thayer, M. P. Di Magliano, P. W. Heiser et al., “Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis,” Nature, vol. 425, no. 6960, pp. 851–856, 2003. View at Publisher · View at Google Scholar · View at Scopus
  12. R. L. Yauch, S. E. Gould, S. J. Scales et al., “A paracrine requirement for Hedgehog signalling in cancer,” Nature, vol. 455, no. 7211, pp. 406–410, 2008. View at Publisher · View at Google Scholar · View at Scopus
  13. N. Dahmane, J. Lee, P. Robins, P. Heller, and A. R. Altaba, “Activation of the transcription factor Gli1 and the sonic Hedgehog signalling pathway in skin tumours,” Nature, vol. 389, no. 6653, pp. 876–881, 1997. View at Publisher · View at Google Scholar · View at Scopus
  14. A. B. Undén, P. G. Zaphiropoulos, K. Bruce, R. Toftgård, and M. Ståhle-Bäckdahl, “Human patched (PTCH) mRNA is overexpressed consistently in tumor cells of both familial and sporadic basal cell carcinoma,” Cancer Research, vol. 57, no. 12, pp. 2336–2340, 1997. View at Google Scholar · View at Scopus
  15. Y. Lee, H. L. Miller, P. Jensen et al., “A molecular fingerprint for medulloblastoma,” Cancer Research, vol. 63, no. 17, pp. 5428–5437, 2003. View at Google Scholar · View at Scopus
  16. C. Raffel, R. B. Jenkins, L. Frederick et al., “Sporadic medulloblastomas contain PTCH mutations,” Cancer Research, vol. 57, no. 5, pp. 842–845, 1997. View at Google Scholar · View at Scopus
  17. H. M. Kronenberg, “Developmental regulation of the growth plate,” Nature, vol. 423, no. 6937, pp. 332–336, 2003. View at Publisher · View at Google Scholar · View at Scopus
  18. B. St-Jacques, M. Hammerschmidt, and A. P. McMahon, “Indian Hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formation,” Genes and Development, vol. 13, no. 16, pp. 2072–2086, 1999. View at Google Scholar · View at Scopus
  19. L. Ho, A. Stojanovski, H. Whetstone et al., “Gli2 and p53 cooperate to regulate IGFBP-3-mediated chondrocyte apoptosis in the progression from benign to malignant cartilage tumors,” Cancer Cell, vol. 16, no. 2, pp. 126–136, 2009. View at Publisher · View at Google Scholar · View at Scopus
  20. S. Hopyan, N. Gokgoz, R. Poon et al., “A mutant PTH/PTHrP type I receptor in enchondromatosis,” Nature Genetics, vol. 30, no. 3, pp. 306–310, 2002. View at Publisher · View at Google Scholar · View at Scopus
  21. T. D. Tiet and B. A. Alman, “Developmental pathways in musculoskeletal neoplasia: involvement of the Indian Hedgehog-parathyroid hormone-related protein pathway,” Pediatric Research, vol. 53, no. 4, pp. 539–543, 2003. View at Publisher · View at Google Scholar · View at Scopus
  22. T. D. Tiet, S. Hopyan, P. Nadesan et al., “Constitutive Hedgehog signaling in chondrosarcoma up-regulates tumor cell proliferation,” The American Journal of Pathology, vol. 168, no. 1, pp. 321–330, 2006. View at Publisher · View at Google Scholar · View at Scopus
  23. W. W. Lo, J. S. Wunder, B. C. Dickson et al., “Involvement and targeted intervention of dysregulated Hedgehog signaling in osteosarcoma,” Cancer, vol. 120, no. 4, pp. 537–547, 2014. View at Publisher · View at Google Scholar
  24. D. R. Cox and D. Oakes, Analysis of Survival Data, Chapman & Hall/CRC, New York, NY, USA, 1984.
  25. D. R. Cox, “Regression models and life-tables,” Journal of the Royal Statistical Society B: Methodological, vol. 34, no. 2, pp. 187–220, 1972. View at Google Scholar
  26. G. Heinze and M. Schemper, “A solution to the problem of monotone likelihood in Cox regression,” Biometrics, vol. 57, no. 1, pp. 114–119, 2001. View at Google Scholar · View at Scopus
  27. J. M. Y. Ng and T. Curran, “The Hedgehog's tale: developing strategies for targeting cancer,” Nature Reviews Cancer, vol. 11, no. 7, pp. 493–501, 2011. View at Publisher · View at Google Scholar · View at Scopus
  28. J. Warzecha, S. Göttig, K. U. Chow et al., “Inhibition of osteosarcoma cell proliferation by the Hedgehog-inhibitor cyclopamine,” Journal of Chemotherapy, vol. 19, no. 5, pp. 554–561, 2007. View at Google Scholar · View at Scopus
  29. M. Hirotsu, T. Setoguchi, H. Sasaki et al., “Smoothened as a new therapeutic target for human osteosarcoma,” Molecular Cancer, vol. 9, article 5, 2010. View at Publisher · View at Google Scholar · View at Scopus
  30. H. Nagao, K. Ijiri, M. Hirotsu et al., “Role of GLI2 in the growth of human osteosarcoma,” Journal of Pathology, vol. 224, no. 2, pp. 169–179, 2011. View at Publisher · View at Google Scholar · View at Scopus
  31. W. Yang, X. Liu, E. Choy, H. Mankin, F. J. Hornicek, and Z. Duan, “Targeting Hedgehog-GLI-2 pathway in osteosarcoma,” Journal of Orthopaedic Research, vol. 31, no. 3, pp. 502–509, 2013. View at Publisher · View at Google Scholar
  32. A. B. Mohseny, Y. Cai, M. Kuijjer et al., “The activities of Smad and Gli mediated signalling pathways in high-grade conventional osteosarcoma,” European Journal of Cancer, vol. 48, no. 18, pp. 3429–3438, 2012. View at Publisher · View at Google Scholar
  33. Y. Mori, T. Okumura, S. Tsunoda, Y. Sakai, and Y. Shimada, “Gli-1 expression is associated with lymph node metastasis and tumor progression in esophageal squamous cell carcinoma,” Oncology, vol. 70, no. 5, pp. 378–389, 2007. View at Publisher · View at Google Scholar · View at Scopus
  34. S. You, J. Zhou, S. Chen et al., “PTCH1, a receptor of Hedgehog signaling pathway, is correlated with metastatic potential of colorectal cancer,” Upsala Journal of Medical Sciences, vol. 115, no. 3, pp. 169–175, 2010. View at Publisher · View at Google Scholar · View at Scopus
  35. C. D. M. Fletcher, K. K. Unni, and F. Mertens, Pathology and Genetics of Tumours of Soft Tissue and Bone, vol. 4, World Health Organization, Lyon, France, 2002.