Table of Contents Author Guidelines Submit a Manuscript
Sarcoma
Volume 2011 (2011), Article ID 276463, 8 pages
http://dx.doi.org/10.1155/2011/276463
Review Article

Mesenchymal Stem Cells and the Origin of Ewing's Sarcoma

1Department of Orthopaedic Oncology (Unit 1448), University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
2Department of Genetics (Unit 1010), University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA

Received 14 July 2010; Accepted 6 September 2010

Academic Editor: Cyril Fisher

Copyright © 2011 Patrick P. Lin 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. L. Ordóñez, D. Osuna, D. Herrero, E. de Álava, and J. Madoz-Gúrpide, “Advances in Ewing's sarcoma research: where are we now and what lies ahead?” Cancer Research, vol. 69, no. 18, pp. 7140–7150, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  2. M. E. Nesbit Jr., E. A. Gehan, E. O. Burgert Jr. et al., “Multimodal therapy for the management of primary, nonmetastatic Ewing's Sarcoma of bone: a long-term follow-up of the first intergroup study,” Journal of Clinical Oncology, vol. 8, no. 10, pp. 1664–1674, 1990. View at Google Scholar · View at Scopus
  3. H. E. Grier, M. D. Krailo, N. J. Tarbell et al., “Addition of ifosfamide and etoposide to standard chemotherapy for Ewing's sarcoma and primitive neuroectodermal tumor of bone,” New England Journal of Medicine, vol. 348, no. 8, pp. 694–701, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  4. C. Rodriguez-Galindo, C. A. Billups, L. E. Kun et al., “Survival after recurrence of ewing tumors: the St. Jude children's research hospital experience, 1979–1999,” Cancer, vol. 94, no. 2, pp. 561–569, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  5. J. Ban, C. Siligan, M. Kreppel, D. Aryee, and H. Kovar, “EWS-FLI1 in Ewing's sarcoma: real targets and collateral damage,” Advances in Experimental Medicine and Biology, vol. 587, pp. 41–52, 2006. View at Google Scholar · View at Scopus
  6. N. Riggi and I. Stamenkovic, “The Biology of Ewing sarcoma,” Cancer Letters, vol. 254, no. 1, pp. 1–10, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  7. H. Kovar, “Context matters: the hen or egg problem in Ewing's sarcoma,” Seminars in Cancer Biology, vol. 15, no. 3, pp. 189–196, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  8. J. A. Toretsky, Y. Connell, L. Neckers, and N. K. Bhat, “Inhibition of EWS-FLI-1 fusion protein with antisense oligodeoxynucleotides,” Journal of Neuro-Oncology, vol. 31, no. 1-2, pp. 9–16, 1997. View at Google Scholar · View at Scopus
  9. K. Tanaka, T. Iwakuma, K. Harimaya, H. Sato, and Y. Iwamoto, “EWS-Fli1 antisense oligodeoxynucleotide inhibits proliferation of human Ewing's sarcoma and primitive neuroectodermal tumor cells,” Journal of Clinical Investigation, vol. 99, no. 2, pp. 239–247, 1997. View at Google Scholar · View at Scopus
  10. A. Üren, O. Tcherkasskaya, and J. A. Toretsky, “Recombinant EWS-FLI1 oncoprotein activates transcription,” Biochemistry, vol. 43, no. 42, pp. 13579–13589, 2004. View at Google Scholar · View at Scopus
  11. W. A. May, M. L. Gishizky, S. L. Lessnick et al., “Ewing sarcoma 11;22 translocation produces a chimeric transcription factor that requires the DNA-binding domain encoded by FLI1 for transformation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 12, pp. 5752–5756, 1993. View at Google Scholar · View at Scopus
  12. S. L. Lessnick, B. S. Braun, C. T. Denny, and W. A. May, “Multiple domains mediate transformation by the Ewing's sarcoma EWS/FLI-1 fusion gene,” Oncogene, vol. 10, no. 3, pp. 423–431, 1995. View at Google Scholar · View at Scopus
  13. Y. Ben-David, E. B. Giddens, and A. Bernstein, “Identification and mapping of a common proviral integration site Fli-1 in erythroleukemia cells induced by Friend murine leukemia virus,” Proceedings of the National Academy of Sciences of the United States of America, vol. 87, no. 4, pp. 1332–1336, 1990. View at Google Scholar · View at Scopus
  14. A. H. L. Truong and Y. Ben-David, “The role of Fli-1 in normal cell function and malignant transformation,” Oncogene, vol. 19, no. 55, pp. 6482–6489, 2000. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  15. L. Cironi, N. Riggi, P. Provero et al., “IGF1 is a common target gene of Ewing's sarcoma fusion proteins in mesenchymal progenitor cells,” PLoS One, vol. 3, no. 7, Article ID e2634, 2008. View at Publisher · View at Google Scholar · View at PubMed
  16. M. R. Sollazzo, M. S. Benassi, G. Magagnoli et al., “Increased c-myc oncogene expression in Ewing's sarcoma: correlation with Ki67 proliferation index,” Tumori, vol. 85, no. 3, pp. 167–173, 1999. View at Google Scholar · View at Scopus
  17. D. Herrero-Martín, D. Osuna, J. L. Ordóñez et al., “Stable interference of EWS-FLI1 in an Ewing sarcoma cell line impairs IGF-1/IGF-1R signalling and reveals TOPK as a new target,” British Journal of Cancer, vol. 101, no. 1, pp. 80–90, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  18. R. Smith, L. A. Owen, D. J. Trem et al., “Expression profiling of EWS/FLI identifies NKX2.2 as a critical target gene in Ewing's sarcoma,” Cancer Cell, vol. 9, no. 5, pp. 405–416, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  19. M. Fukuma, H. Okita, J.-I. Hata, and A. Umezawa, “Upregulation of Id2, an oncogenic helix-loop-helix protein, is mediated by the chimeric EWS/ets protein in Ewing sarcoma,” Oncogene, vol. 22, no. 1, pp. 1–9, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  20. E. García-Aragoncillo, J. Carrillo, E. Lalli et al., “DAX1, a direct target of EWS/FLI1 oncoprotein, is a principal regulator of cell-cycle progression in Ewing's tumor cells,” Oncogene, vol. 27, no. 46, pp. 6034–6043, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  21. J. P. Zwerner, J. Joo, K. L. Warner et al., “The EWS/FLI1 oncogenic transcription factor deregulates GLI1,” Oncogene, vol. 27, no. 23, pp. 3282–3291, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  22. G. H. S. Richter, S. Plehm, A. Fasan et al., “EZH2 is a mediator of EWS/FLI1 driven tumor growth and metastasis blocking endothelial and neuro-ectodermal differentiation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 13, pp. 5324–5329, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  23. C. Siligan, J. Ban, R. Bachmaier et al., “EWS-FLI1 target genes recovered from Ewing's sarcoma chromatin,” Oncogene, vol. 24, no. 15, pp. 2512–2524, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  24. R. Kikuchi, M. Murakami, S. Sobue et al., “Ewing's sarcoma fusion protein, EWS/Fli-1 and Fli-1 protein induce PLD2 but not PLD1 gene expression by binding to an ETS domain of 5' promoter,” Oncogene, vol. 26, no. 12, pp. 1802–1810, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  25. K.-B. Hahm, K. Cho, C. Lee et al., “Repression of the gene encoding the TGF-β type II receptor is a major target of the EWS-FLI1 oncoprotein,” Nature Genetics, vol. 23, no. 2, pp. 222–227, 1999. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  26. F. Nakatani, K. Tanaka, R. Sakimura et al., “Identification of p21WAF1/CIP1 as a direct target of EWS-Fli1 oncogenic fusion protein,” Journal of Biological Chemistry, vol. 278, no. 17, pp. 15105–15115, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  27. L. Dauphinot, C. De Oliveira, T. Melot et al., “Analysis of the expression of cell cycle regulators in Ewing cell lines: EWS-FLI-1 modulates p57KIP2 and c-Myc expression,” Oncogene, vol. 20, no. 25, pp. 3258–3265, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  28. A. Prieur, F. Tirode, P. Cohen, and O. Delattre, “EWS/FLI-1 silencing and gene profiling of Ewing cells reveal downstream oncogenic pathways and a crucial role for repression of insulin-like growth factor binding protein 3,” Molecular and Cellular Biology, vol. 24, no. 16, pp. 7275–7283, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  29. N. Riggi, M.-L. Suvà, C. De Vito et al., “EWS-FLI-1 modulates miRNA145 and SOX2 expression to initiate mesenchymal stem cell reprogramming toward Ewing sarcoma cancer stem cells,” Genes and Development, vol. 24, no. 9, pp. 916–932, 2010. View at Publisher · View at Google Scholar · View at PubMed
  30. L. Yang, H. A. Chansky, and D. D. Hickstein, “EWS·Fli-1 fusion protein interacts with hyperphosphorylated RNA polymerase II and interferes with serine-arginine protein-mediated RNA splicing,” Journal of Biological Chemistry, vol. 275, no. 48, pp. 37612–37618, 2000. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  31. J. A. Toretsky, V. Erkizan, A. Levenson et al., “Oncoprotein EWS-FLI1 activity is enhanced by RNA helicase A,” Cancer Research, vol. 66, no. 11, pp. 5574–5581, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  32. H. A. Chansky, M. Hu, D. D. Hickstein, and L. Yang, “Oncogenic TLS/ERG and EWS/Fli-1 fusion proteins inhibit RNA splicing mediated by YB-1 protein,” Cancer Research, vol. 61, no. 9, pp. 3586–3590, 2001. View at Google Scholar · View at Scopus
  33. D. M. Gascoyne, G. R. Thomas, and D. S. Latchman, “The effects of Brn-3a on neuronal differentiation and apoptosis are differentially modulated by EWS and its oncogenic derivative EWS/Fli-1,” Oncogene, vol. 23, no. 21, pp. 3830–3840, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  34. S. Kim, C. T. Denny, and R. Wisdom, “Cooperative DNA binding with AP-1 proteins is required for transformation by EWS-Ets fusion proteins,” Molecular and Cellular Biology, vol. 26, no. 7, pp. 2467–2478, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  35. R. Petermann, B. M. Mossier, D. N. T. Aryee, V. Khazak, E. A. Golemis, and H. Kovar, “Oncogenic EWS-Fli1 interacts with hsRPB7, a subunit of human RNA polymerase II,” Oncogene, vol. 17, no. 5, pp. 603–610, 1998. View at Google Scholar · View at Scopus
  36. L. Spahn, R. Petermann, C. Siligan, J. A. Schmid, D. N. T. Aryee, and H. Kovar, “Interaction of the EWS NH2 terminus with BARD1 links the Ewing's sarcoma gene to a common tumor suppressor pathway,” Cancer Research, vol. 62, no. 16, pp. 4583–4587, 2002. View at Google Scholar · View at Scopus
  37. D. K. Watson, L. Robinson, D. R. Hodge, I. Kola, T. S. Papas, and A. Seth, “FLI1 and EWS-FLI1 function as ternary complex factors and ELK1 and SAP1a function as ternary and quaternary complex factors on the Egr1 promoter serum response elements,” Oncogene, vol. 14, no. 2, pp. 213–221, 1997. View at Google Scholar · View at Scopus
  38. B. Deneen and C. T. Denny, “Loss of p16 pathways stabilizes EWS/FLI1 expression and complements EWS/FLI1 mediated transformation,” Oncogene, vol. 20, no. 46, pp. 6731–6741, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  39. S. L. Lessnick, C. S. Dacwag, and T. R. Golub, “The Ewing's sarcoma oncoprotein EWS/FLI induces a p53-dependent growth arrest in primary human fibroblasts,” Cancer Cell, vol. 1, no. 4, pp. 393–401, 2002. View at Publisher · View at Google Scholar · View at Scopus
  40. A. O. Cavazzana, J. S. Miser, J. Jefferson, and T. J. Triche, “Experimental evidence for a neural origin of Ewing's sarcoma of bone,” American Journal of Pathology, vol. 127, no. 3, pp. 507–518, 1987. View at Google Scholar · View at Scopus
  41. C.-H. Suh, N. G. Ordóñez, J. Hicks, and B. Mackay, “Ultrastructure of the Ewing's sarcoma family of tumors,” Ultrastructural Pathology, vol. 26, no. 2, pp. 67–76, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  42. W. J. Rettig, P. Garin-Chesa, and A. G. Huvos, “Ewing's sarcoma: new approaches to histogenesis and molecular plasticity,” Laboratory Investigation, vol. 66, no. 2, pp. 133–137, 1992. View at Google Scholar · View at Scopus
  43. A. Franchi, G. Pasquinelli, G. Cenacchi et al., “Immunohistochemical and ultrastructural investigation of neural differentiation in Ewing sarcoma/PNET of bone and soft tissues,” Ultrastructural Pathology, vol. 25, no. 3, pp. 219–225, 2001. View at Google Scholar · View at Scopus
  44. S. Navarro, M. Gonzalez-Devesa, A. Ferrandez-Izquierdo, T. J. Triche, and A. Llombart-Bosch, “Scanning electron microscopic evidence for neural differentiation in Ewing's sarcoma cell lines,” Virchows Archiv A, vol. 416, no. 5, pp. 383–391, 1990. View at Google Scholar · View at Scopus
  45. C. J. Rorie, V. D. Thomas, P. Chen, H. H. Pierce, J. P. O'Bryan, and B. E. Weissman, “The Ews/Fli-1 fusion gene switches the differentiation program of neuroblastomas to Ewing sarcoma/peripheral primitive neuroectodermal tumors,” Cancer Research, vol. 64, no. 4, pp. 1266–1277, 2004. View at Publisher · View at Google Scholar · View at Scopus
  46. M. A. Teitell, A. D. Thompson, P. H. B. Sorensen, H. Shimada, T. J. Triche, and C. T. Denny, “EWS/ETS fusion genes induce epithelial and neuroectodermal differentiation in NIH 3T3 fibroblasts,” Laboratory Investigation, vol. 79, no. 12, pp. 1535–1543, 1999. View at Google Scholar · View at Scopus
  47. S. Hu-Lieskovan, J. Zhang, L. Wu, H. Shimada, D. E. Schofield, and T. J. Triche, “EWS-FLI1 fusion protein up-regulates critical genes in neural crest development and is responsible for the observed phenotype of Ewing's family of tumors,” Cancer Research, vol. 65, no. 11, pp. 4633–4644, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  48. Y. Takashima, T. Era, K. Nakao et al., “Neuroepithelial cells supply an initial transient wave of MSC differentiation,” Cell, vol. 129, no. 7, pp. 1377–1388, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  49. B. R. Olsen, A. M. Reginato, and W. Wang, “Bone development,” Annual Review of Cell and Developmental Biology, vol. 16, pp. 191–220, 2000. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  50. E. C. Torchia, S. Jaishankar, and S. J. Baker, “Ewing tumor fusion proteins block the differentiation of pluripotent marrow stromal cells,” Cancer Research, vol. 63, no. 13, pp. 3464–3468, 2003. View at Google Scholar · View at Scopus
  51. G. C. Kopen, D. J. Prockop, and D. G. Phinney, “Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 19, pp. 10711–10716, 1999. View at Publisher · View at Google Scholar · View at Scopus
  52. D. Woodbury, E. J. Schwarz, D. J. Prockop, and I. B. Black, “Adult rat and human bone marrow stromal cells differentiate into neurons,” Journal of Neuroscience Research, vol. 61, no. 4, pp. 364–370, 2000. View at Publisher · View at Google Scholar · View at Scopus
  53. P. Bianco, P. G. Robey, and P. J. Simmons, “Mesenchymal stem cells: revisiting history, concepts, and assays,” Cell Stem Cell, vol. 2, no. 4, pp. 313–319, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  54. N. Beyer Nardi and L. da Silva Meirelles, “Mesenchymal stem cells: isolation, in vitro expansion and characterization,” Handbook of Experimental Pharmacology, no. 174, pp. 249–282, 2006. View at Google Scholar · View at Scopus
  55. W. R. Otto and J. Rao, “Tomorrow's skeleton staff: mesenchymal stem cells and the repair of bone and cartilage,” Cell Proliferation, vol. 37, no. 1, pp. 97–110, 2004. View at Publisher · View at Google Scholar · View at Scopus
  56. R. J. Deans and A. B. Moseley, “Mesenchymal stem cells: biology and potential clinical uses,” Experimental Hematology, vol. 28, no. 8, pp. 875–884, 2000. View at Publisher · View at Google Scholar · View at Scopus
  57. T. A. Lodie, C. E. Blickarz, T. J. Devarakonda et al., “Systematic analysis of reportedly distinct populations of multipotent bone marrow-derived stem cells reveals a lack of distinction,” Tissue Engineering, vol. 8, no. 5, pp. 739–751, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  58. F. Anjos-Afonso, E. K. Siapati, and D. Bonnet, “In vivo contribution of murine mesenchymal stem cells into multiple cell-types under minimal damage conditions,” Journal of Cell Science, vol. 117, no. 23, pp. 5655–5664, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  59. D. J. Prockop, “Marrow stromal cells as stem cells for nonhematopoietic tissues,” Science, vol. 276, no. 5309, pp. 71–74, 1997. View at Publisher · View at Google Scholar · View at Scopus
  60. D. C. Colter, I. Sekiya, and D. J. Prockop, “Identification of a subpopulation of rapidly self-renewing and multipotential adult stem cells in colonies of human marrow stromal cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 14, pp. 7841–7845, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  61. Y. Jiang, B. N. Jahagirdar, R. L. Reinhardt et al., “Pluripotency of mesenchymal stem cells derived from adult marrow,” Nature, vol. 418, no. 6893, pp. 41–49, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  62. A. P. Beltrami, D. Cesselli, N. Bergamin et al., “Multipotent cells can be generated in vitro from several adult human organs (heart, liver, and bone marrow),” Blood, vol. 110, no. 9, pp. 3438–3446, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  63. F. Tirode, K. Laud-Duval, A. Prieur, B. Delorme, P. Charbord, and O. Delattre, “Mesenchymal stem cell features of Ewing tumors,” Cancer Cell, vol. 11, no. 5, pp. 421–429, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  64. Y. Castillero-Trejo, S. Eliazer, L. Xiang, J. A. Richardson, and R. L. Ilaria Jr., “Expression of the EWS/FLI-1 oncogene in murine primary bone-derived cells results in EWS/FLI-1-dependent, Ewing sarcoma-like tumors,” Cancer Research, vol. 65, no. 19, pp. 8698–8705, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  65. N. Riggi, L. Cironi, P. Provero et al., “Development of Ewing's sarcoma from primary bone marrow-derived mesenchymal progenitor cells,” Cancer Research, vol. 65, no. 24, pp. 11459–11468, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  66. I. González, S. Vicent, E. de Alava, and F. Lecanda, “EWS/FLI-1 oncoprotein subtypes impose different requirements for transformation and metastatic activity in a murine model,” Journal of Molecular Medicine, vol. 85, no. 9, pp. 1015–1029, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  67. N. Riggi, M.-L. Suvà, D. Suvà et al., “EWS-FLI-1 expression triggers a ewing's sarcoma initiation program in primary human mesenchymal stem cells,” Cancer Research, vol. 68, no. 7, pp. 2176–2185, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  68. J. M. Funes, M. Quintero, S. Henderson et al., “Transformation of human mesenchymal stem cells increases their dependency on oxidative phosphorylation for energy production,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 15, pp. 6223–6228, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  69. Y. F. Zhou, M. Bosch-Marce, H. Okuyama et al., “Spontaneous transformation of cultured mouse bone marrow-derived stromal cells,” Cancer Research, vol. 66, no. 22, pp. 10849–10854, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  70. Y. Miyagawa, H. Okita, H. Nakaijima et al., “Inducible expression of chimeric EWS/ETS proteins confers Ewing's family tumor-like phenotypes to human mesenchymal progenitor cells,” Molecular and Cellular Biology, vol. 28, no. 7, pp. 2125–2137, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  71. H. Kovar and A. Bernard, “CD99-positive “Ewing's sarcoma” from mouse bone marrow-derived mesenchymal progenitor cells?” Cancer Research, vol. 66, no. 19, p. 9786, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  72. J. S. Burns, B. M. Abdallah, H. D. Shrøder, and M. Kassem, “The histopathology of a human mesenchymal stem cell experimental tumor model: support for an hMSC origin for Ewing's sarcoma?” Histology and Histopathology, vol. 23, no. 10, pp. 1229–1240, 2008. View at Google Scholar
  73. A. Llombart-Bosch, I. Machado, S. Navarro et al., “Histological heterogeneity of Ewing's sarcoma/PNET: an immunohistochemical analysis of 415 genetically confirmed cases with clinical support,” Virchows Archiv, vol. 455, no. 5, pp. 397–411, 2009. View at Publisher · View at Google Scholar · View at PubMed
  74. O. M. Tirado, S. Mateo-Lozano, J. Villar et al., “Caveolin-1 (CAV1) is a target of EWS/FLI-1 and a key determinant of the oncogenic phenotype and tumorigenicity of Ewing's sarcoma cells,” Cancer Research, vol. 66, no. 20, pp. 9937–9947, 2006. View at Publisher · View at Google Scholar · View at PubMed
  75. G. Potikyan, K. A. France, M. R. J. Carlson, J. Dong, S. F. Nelson, and C. T. Denny, “Genetically defined EWS/FLI1 model system suggests mesenchymal origin of Ewing's family tumors,” Laboratory Investigation, vol. 88, no. 12, pp. 1291–1302, 2008. View at Publisher · View at Google Scholar · View at PubMed
  76. J. D. Hancock and S. L. Lessnick, “A transcriptional profiling meta-analysis reveals a core EWS-FLI gene expression signature,” Cell Cycle, vol. 7, no. 2, pp. 250–256, 2008. View at Google Scholar
  77. E. J. Sohn, H. Li, K. Reidy, L. F. Beers, B. L. Christensen, and S. B. Lee, “EWS/FLI1 oncogene activates caspase 3 transcription and triggers apoptosis in vivo,” Cancer Research, vol. 70, no. 3, pp. 1154–1163, 2010. View at Publisher · View at Google Scholar · View at PubMed
  78. E. C. Torchia, K. Boyd, J. E. Rehg, C. Qu, and S. J. Baker, “EWS/FLI-1 induces rapid onset of myeloid/erythroid leukemia in mice,” Molecular and Cellular Biology, vol. 27, no. 22, pp. 7918–7934, 2007. View at Publisher · View at Google Scholar · View at PubMed
  79. P. P. Lin, M. K. Pandey, F. Jin et al., “EWS-FLI1 induces developmental abnormalities and accelerates sarcoma formation in a transgenic mouse model,” Cancer Research, vol. 68, no. 21, pp. 8968–8975, 2008. View at Publisher · View at Google Scholar · View at PubMed
  80. R. Kuhn, F. Schwenk, M. Aguet, and K. Rajewsky, “Inducible gene targeting in mice,” Science, vol. 269, no. 5229, pp. 1427–1429, 1995. View at Google Scholar
  81. R. Codrington, R. Pannell, A. Forster et al., “The Ews-ERG fusion protein can initiate neoplasia from lineage-committed haematopoietic cells,” PLoS Biology, vol. 3, no. 8, article e242, 2005. View at Publisher · View at Google Scholar · View at PubMed
  82. M. P. McCormack, A. Forster, L. Drynan, R. Pannell, and T. H. Rabbitts, “The LMO2 T-cell oncogene is activated via chromosomal translocations or retroviral insertion during gene therapy but has no mandatory role in normal T-cell development,” Molecular and Cellular Biology, vol. 23, no. 24, pp. 9003–9013, 2003. View at Publisher · View at Google Scholar
  83. G. Jakovljević, M. Nakić, S. Rogošić et al., “Pre-B-cell acute lymphoblastic leukemia with bulk extramedullary disease and chromosome 22 (EWSR1) rearrangement masquerading as ewing sarcoma,” Pediatric Blood and Cancer, vol. 54, no. 4, pp. 606–609, 2010. View at Publisher · View at Google Scholar · View at PubMed
  84. A. Martini, R. La Starza, H. Janssen et al., “Recurrent rearrangement of the Ewing's sarcoma gene, EWSR1, or its homologue, TAF15, with the transcription factor CIZ/NMP4 in acute leukemia,” Cancer Research, vol. 62, no. 19, pp. 5408–5412, 2002. View at Google Scholar
  85. G. Marcucci, C. D. Baldus, A. S. Ruppert et al., “Overexpression of the ETS-related gene, ERG, predicts a worse outcome in acute myeloid leukemia with normal karyotype: a Cancer and Leukemia Group B study,” Journal of Clinical Oncology, vol. 23, no. 36, pp. 9234–9242, 2005. View at Publisher · View at Google Scholar · View at PubMed
  86. J. M. Hawkins, J. M. Craig, L. M. Secker-Walker, H. G. Prentice, and A. B. Mehta, “Ewing's sarcoma t(11;22) in a case of acute nonlymphocytic leukemia,” Cancer Genetics and Cytogenetics, vol. 55, no. 2, pp. 157–162, 1991. View at Publisher · View at Google Scholar
  87. K. Haresh, N. Joshi, C. Gupta et al., “Granulocytic sarcoma masquerading as Ewing's sarcoma: a diagnostic dilemma,” Journal of Cancer Research and Therapeutics, vol. 4, no. 3, pp. 137–139, 2008. View at Publisher · View at Google Scholar
  88. P. H. B. Sorensen, H. Shimada, X. F. Liu, J. F. Lim, G. Thomas, and T. J. Triche, “Biphenotypic sarcomas with myogenic and neural differentiation express the Ewing's sarcoma EWS/FLI1 fusion gene,” Cancer Research, vol. 55, no. 6, pp. 1385–1392, 1995. View at Google Scholar
  89. C. Aussel, G. Bernard, J.-P. Breittmayer, C. Pelassy, D. Zoccola, and A. Bernard, “Monoclonal antibodies directed against the E2 protein (MIC2 gene product) induce exposure of phosphatidylserine at the thymocyte cell surface,” Biochemistry, vol. 32, no. 38, pp. 10096–10101, 1993. View at Publisher · View at Google Scholar
  90. C. Keller, B. R. Arenkiel, C. M. Coffin, N. El-Bardeesy, R. A. DePinho, and M. R. Capecchi, “Alveolar rhabdomyosarcomas in conditional Pax3:Fkhr mice: cooperativity of Ink4a/ARF and Trp53 loss of function,” Genes and Development, vol. 18, no. 21, pp. 2614–2626, 2004. View at Publisher · View at Google Scholar · View at PubMed
  91. H. Y. Huang, P. B. Illei, Z. Zhao et al., “Ewing sarcomas with p53 mutation or p16/p14ARF homozygous deletion: a highly lethal subset associated with poor chemoresponse,” Journal of Clinical Oncology, vol. 23, no. 3, pp. 548–558, 2005. View at Google Scholar