Cancer stem cells and pediatric solid tumors

Cancers

Volumn 3, Issue 1, 2011, Pages 298-318

  Friedman, Gregory K ^a   Gillespie, G Yancey ^b  

^a University of Alabama at Birmingham   (United States)

^b Kentucky   (United States)

Author keywords

Cancer initiating cells, tumor stem cells; Cancer progenitor cells; Cancer stem cells; CD133; Children; Pediatrics; Tumor initiating cells; Tumor progenitor cells

Indexed keywords

ABC TRANSPORTER; CARBOPLATIN; CD133 ANTIGEN; CD20 ANTIGEN; CD24 ANTIGEN; CISPLATIN; DOXORUBICIN; ETOPOSIDE; GELATINASE B; HERMES ANTIGEN; KI 67 ANTIGEN; NESTIN; NOTCH RECEPTOR; STEM CELL FACTOR RECEPTOR; THY 1 ANTIGEN; TUMOR MARKER; VASCULOTROPIN;

BRAIN TUMOR; CANCER RESISTANCE; CANCER STEM CELL; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL DIFFERENTIATION; CELL PROLIFERATION; CELL RENEWAL; CHEMOSENSITIVITY; DNA DAMAGE; EMBRYONIC STEM CELL; EPENDYMOMA; GLIOBLASTOMA; HERPES SIMPLEX VIRUS; HUMAN; IMMUNOPHENOTYPING; MEDULLOBLASTOMA; NONHUMAN; PEDIATRICS; PROTEIN EXPRESSION; REVIEW; RHABDOID TUMOR; SOLID TUMOR; TARGET CELL DESTRUCTION; TUMOR MICROENVIRONMENT; VIROTHERAPY;

EID: 79953699989     PISSN: None     EISSN: 20726694     Source Type: Journal    
DOI: 10.3390/cancers3010298     Document Type: Review

References (112)

1. Ries, L.A.G., Melbert D., Krapcho M., Mariotto A., Miller B.A., Feuer E.J., et al. SEER Cancer Statistics Review, 1975-2004; National Cancer Institute: Bethesda, MD, USA, 2006; Available online at: http://seer.cancer.gov/csr/1975_2004/ (accessed on 14 January 2011).
2. Gatta, G.; Capocaccia, R.; Coleman, M.P.; Ries, L.A.; Berrino, F. Childhood cancer survival in Europe and the United States. Cancer 2002, 95, 1767-1772.
3. Al-Hajj, M.; Wicha, M.S.; Benito-Hernandez, A.; Morrison, S.J.; Clarke, M.F. Prospective identification of tumorigenic breast cancer cells. Proc. Natl. Acad. Sci. USA 2003, 100, 3983-3988.
4. Singh, S.K.; Clarke, I.D.; Terasaki, M.; Bonn, V.E.; Hawkins, C.; Squire, J.; Dirks, P.B. Identification of a cancer stem cell in human brain tumors. Cancer Res. 2003, 63, 5821-5828.
5. Eramo, A.; Lotti, F.; Sette, G.; Pilozzi, E.; Biffoni, M.; Di Virgilio, A.; Conticello, C.; Ruco, L.; Peschle, C.; De Maria, R. Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Difer. 2008, 15, 504-514.
6. Collins, A.T.; Berry, P.A.; Hyde, C.; Stower, M.J.; Maitland, N.J. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res. 2005, 65, 10946-10951.
7. Fang, D.; Nguyen, T.K.; Leishear, K.; Finko, R.; Kulp, A.N.; Hotz, S.; Van Belle, P.A.; Xu, X.; Elder, D.E.; Herlyn, M.A. tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res. 2005, 65, 9328-9337.
8. Li, C.; Heidt, D.G.; Dalerba, P.; Burant, C.F.; Zhang, L.; Adsay, V.; Wicha, M.; Clarke, M.F.; Simeone, D.M. Identification of pancreatic cancer stem cells. Cancer Res. 2007, 67, 1030-1037.
9. O'Brien, C.A.; Pollett, A.; Gallinger, S.; Dick, J.E. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 2007, 445, 106-110.
10. Suetsugu, A.; Nagaki, M.; Aoki, H.; Motohashi, T.; Kunisada, T.; Moriwaki, H. Characterization of CD1 33+ hepatocellular carcinoma cells as cancer stem/progenitor cells. Biochem. Biophys. Res. Commun. 2006, 351, 820-824.
11. Prince, M.E.; Sivanandan, R.; Kaczorowski, A.; Wolf, G.T.; Kaplan, M.J.; Dalerba, P.; Weissman, I.L.; Clarke, M.F.; Ailles, L.E. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc. Natl. Acad. Sci. USA 2007, 104, 973-978.
12. Szotek, P.P.; Pieretti-Vanmarcke, R.; Masiakos, P.T.; Dinulescu, D.M.; Connolly, D.; Foster, R.; Dombkowski, D.; Preffer, F.; Maclaughlin, D.T.; Donahoe, P.K. Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian Inhibiting Substance responsiveness. Proc. Natl. Acad. Sci. USA 2006, 103, 11154-11159.
13. Vlashi, E.; McBride, W.H.; Pajonk, F. Radiation responses of cancer stem cells. J. Cell Biochem. 2009, 108, 339-342.
14. Rich, J.N.; Bao, S. Chemotherapy and cancer stem cells. Cell Stem Cell 2007, 1, 353-355.
15. Garvalov, B.K.; Acker, T. Cancer stem cells: A new framework for the design of tumor therapies. J. Mol. Med. 2010, 2, doi:10.1007/s00109-010-0685-3.
16. Dhodapkar, M.V. Immunity to stemness genes in human cancer. Curr. Opin. Immunol. 2010, 22, 245-250.
17. Saini, V.; Shoemaker, R.H. Potential for therapeutic targeting of tumor stem cells. Cancer Sci. 2010, 101, 16-21.
18. Frank, N.Y.; Schatton, T.; Frank, M.H. The therapeutic promise of the cancer stem cell concept. J. Clin. Invest. 2010, 120, 41-50.
19. Fomchenko, E.I.; Holland, E.C. Platelet-derived growth factor-mediated gliomagenesis and brain tumor recruitment. Neurosurg. Clin. N. Am. 2007, 18, 39-58.
20. Fábián, A.; Barok, M.; Vereb, G.; Szöllosi, J. Die hard: Are cancer stem cells the Bruce Willises of tumor biology? Cytometry A. 2009, 75, 67-74.
21. Hill, R.P. Identifying cancer stem cells in solid tumors: Case not proven. Cancer Res. 2006, 66, 1891-1895.
22. Yin, A.H.; Miraglia, S.; Zanjani, E.D.; Almeida-Porada, G.; Ogawa, M.; Leary, A.G.; Olweus, J.; Kearney, J.; Buck, D.W. AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood 1997, 90, 5002-5012.
23. Miraglia, S.; Godfrey, W.; Yin, A.H.; Atkins, K.; Warnke, R.; Holden, J.T.; Bray, R.A.; Waller, E.K.; Buck, D.W. A novel five-transmembrane hematopoietic stem cell antigen: Isolation, characterization, and molecular cloning. Blood 1997, 90, 5013-5021.
24. Singh, S.K.; Clarke, I.D.; Terasaki, M.; Bonn, V.E.; Hawkins, C.; Squire, J.; Dirks, P.B. Identification of a cancer stem cell in human brain tumors. Cancer Res. 2003, 63, 5821-5828.
25. Hemmati, H.D.; Nakano, I.; Lazareff, J.A.; Masterman-Smith, M.; Geschwind, D.H.; Bronner-Fraser, M.; Kornblum, H.I. Cancerous stem cells can arise from pediatric brain tumors. Proc. Natl. Acad. Sci. USA 2003, 100, 15178-15183.
26. Li, M.C.; Deng, Y.W.; Wu, J.; Chen, F.H.; Liu, J.F.; Fang, J.S. Isolation and characterization of brain tumor stem cells in human medulloblastoma. Ai Zheng 2006, 25, 241-246.
27. Raso, A.; Negri, F.; Gregorio, A.; Nozza, P.; Mascelli, S.; De Marco, P.; Merello, E.; Milanaccio, C.; Ravegnani, M.; Cama, A.; Garrè, M.L.; Capra, V. Successful isolation and long-term establishment of a cell line with stem cell-like features from an anaplastic medulloblastoma. Neuropathol. Appl. Neurobiol. 2008, 34, 306-315.
28. Shu, Q.; Wong, K.K.; Su, J.M.; Adesina, A.M.; Yu, L.T.; Tsang, Y.T.; Antalffy, B.C.; Baxter, P.; Perlaky, L.; Yang, J.; Dauser, R.C.; Chintagumpala, M.; Blaney, S.M.; Lau, C.C.; Li, X.N. Direct orthotopic transplantation of fresh surgical specimen preserves CD133+ tumor cells in clinically relevant mouse models of medulloblastoma and glioma. Stem Cells 2008, 26, 1414-1424.
29. Taylor, M.D.; Poppleton, H.; Fuller, C.; Su, X.; Liu, Y.; Jensen, P.; Magdaleno, S.; Dalton, J.; Calabrese, C.; Board, J.; Macdonald, T.; Rutka, J.; Guha, A.; Gajjar, A.; Curran, T.; Gilbertson, R.J. Radial glia cells are candidate stem cells of ependymoma. Cancer Cell 2005, 8, 323-335.
30. Yu, L.; Baxter, P.A.; Voicu, H.; Gurusiddappa, S.; Zhao, Y.; Adesina, A.; Man, T.K.; Shu, Q.; Zhang, Y.J.; Zhao, X.M.; Su, J.M.; Perlaky, L.; Dauser, R.; Chintagumpala, M.; Lau, C.C.; Blaney, S.M.; Rao, P.H.; Leung, H.C.; Li, X.N. A clinically relevant orthotopic xenograft model of ependymoma that maintains the genomic signature of the primary tumor and preserves cancer stem cells in vivo. Neuro. Oncol. 2010, 12. 580-594.
31. Chiou, S.H.; Kao, C.L.; Chen, Y.W.; Chien, C.S.; Hung, S.C.; Lo, J.F.; Chen, Y.J.; Ku, H.H.; Hsu, M.T.; Wong, T.T. Identification of CD133-positive radioresistant cells in atypical teratoid/rhabdoid tumor. PLoS One 2008, 3, e2090.
32. Mao, X.G.; Zhang, X.; Xue, X.Y.; Guo, G.; Wang, P.; Zhang, W.; Fei, Z.; Zhen, H.N.; You, S.W.; Yang, H. Brain Tumor Stem-Like Cells Identified by Neural Stem Cell Marker CD15. Transl Oncol 2009, 2, 247-257.
33. Ward, R.J.; Lee, L.; Graham, K.; Satkunendran, T.; Yoshikawa, K.; Ling, E.; Harper, L.; Austin, R.; Nieuwenhuis, E.; Clarke, I.D.; Hui, C.C.; Dirks, P.B. Multipotent CD15+ cancer stem cells in patched-1-deficient mouse medulloblastoma. Cancer Res. 2009, 69, 4682-4690.
34. Read, T.A.; Fogarty, M.P.; Markant, S.L.; McLendon, R.E.; Wei, Z.; Ellison, D.W.; Febbo, P.G.; Wechsler-Reya, R.J. Identification of CD15 as a marker for tumor-propagating cells in a mouse model of medulloblastoma. Cancer Cell 2009, 15, 135-147.
35. Capela, A.; Temple, S. LeX is expressed by principle progenitor cells in the embryonic nervous system, is secreted into their environment and binds Wnt-1. Dev. Biol. 2006, 291, 300-313.
36. Zhong, X.; Li, Y.; Peng, F.; Huang, B.; Lin, J.; Zhang, W.; Zheng, J.; Jiang, R.; Song, G.; Ge, J. Identification of tumorigenic retinal stem-like cells in human solid retinoblastomas. Int. J. Cancer 2007, 121, 2125-2131.
37. Seigel, G.M.; Hackam, A.S.; Ganguly, A.; Mandell, L.M.; Gonzalez-Fernandez, F. Human embryonic and neuronal stem cell markers in retinoblastoma. Mol. Vis. 2007, 13, 823-832.
38. Seigel, G.M.; Campbell, L.M.; Narayan, M.; Gonzalez-Fernandez, F. Cancer stem cell characteristics in retinoblastoma. Mol. Vis. 2005, 11, 729-737.
39. Balla, M.M.; Vemuganti, G.K.; Kannabiran, C.; Honavar, S.G.; Murthy, R. Phenotypic characterization of retinoblastoma for the presence of putative cancer stem-like cell markers by flow cytometry. Invest. Ophthalmol. Vis. Sci. 2009, 50, 1506-1514.
40. Li, C.; Heidt, D.G.; Dalerba, P.; Burant, C.F.; Zhang, L.; Adsay, V.; Wicha, M.; Clarke, M.F.; Simeone, D.M. Identification of pancreatic cancer stem cells. Cancer Res. 2007, 67, 1030-1037.
41. Ponti, D.; Costa, A.; Zaffaroni, N.; Pratesi, G.; Petrangolini, G.; Coradini, D.; Pilotti, S.; Pierotti, M.A.; Daidone, M.G. Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res. 2005, 65, 5506-5511.
42. Mahller, Y.Y.; Williams, J.P.; Baird, W.H.; Mitton, B.; Grossheim, J.; Saeki, Y.; Cancelas, J.A.; Ratner, N.; Cripe, T.P. Neuroblastoma cell lines contain pluripotent tumor initiating cells that are susceptible to a targeted oncolytic virus. PLoS One 2009, 4, e4235.
43. Tong, Q.S.; Zheng, L.D.; Tang, S.T.; Ruan, Q.L.; Liu, Y.; Li, S.W.; Jiang, G.S.; Cai, J.B. Expression and clinical significance of stem cell marker CD 133 in human neuroblastoma. World J. Pediatr. 2008, 4, 58-62.
44. Al Dhaybi, R.; Sartelet, H.; Powell, J.; Kokta, V. Expression of CD133+ cancer stem cells in childhood malignant melanoma and its correlation with metastasis. Mod. Pathol. 2010, 23, 376-380.
45. Yanagisawa, S.; Kadouchi, I.; Yokomori, K.; Hirose, M.; Hakozaki, M.; Hojo, H.; Maeda, K.; Kobayashi, E.; Murakami, T. Identification and metastatic potential of tumor-initiating cells in malignant rhabdoid tumor of the kidney. Clin. Cancer Res. 2009, 15, 3014-3022.
46. Pode-Shakked, N.; Metsuyanim, S.; Rom-Gross, E.; Mor, Y.; Fridman, E.; Goldstein, I.; Amariglio, N.; Rechavi, G.; Keshet, G.; Dekel, B. Developmental Tumorigenesis: NCAM as a putative marker for the malignant renal stem/progenitor cell population. J. Cell Mol. Med. 2008, 13, doi:10.1111/j.1582-4934.2008.00607.x.
47. Abbate, M.; Brown, D.; Bonventre, J.V. Expression of NCAM recapitulates tubulogenic development in kidneys recovering from acute ischemia. Am. J. Physiol. 1999, 277, F454-F463.
48. Tirino, V.; Desiderio, V.; d'Aquino, R.; De Francesco, F.; Pirozzi, G.; Graziano, A.; Galderisi, U.; Cavaliere, C.; De Rosa, A.; Papaccio, G.; Giordano, A. Detection and characterization of CD133+ cancer stem cells in human solid tumours. PLoS One 2008, 3, e3469.
49. Veselska, R.; Hermanova, M.; Loja, T.; Chlapek, P.; Zambo, I.; Vesely, K.; Zitterbart, K.; Sterba, J. Nestin expression in osteosarcomas and derivation of nestin/CD133 positive osteosarcoma cell lines. BMC Cancer 2008, 8, 300.
50. Wang, L.; Park, P.; Lin, C.Y. Characterization of stem cell attributes in human osteosarcoma cell lines. Cancer Biol. Ther. 2009, 8, 543-552.
51. Di Fiore, R.; Santulli, A.; Ferrante, R.D.; Giuliano, M.; De Blasio, A.; Messina, C.; Pirozzi, G.; Tirino, V.; Tesoriere, G.; Vento, R. Identification and expansion of human osteosarcoma-cancer-stem cells by long-term 3-aminobenzamide treatment. J. Cell Physiol. 2009, 219, 301-313.
52. Hettmer, S.; Wagers, A.J. Muscling in: Uncovering the origins of rhabdomyosarcoma. Nat. Med. 2010, 16, 171-173.
53. Charytonowicz, E.; Cordon-Cardo, C.; Matushansky, I.; Ziman, M. Alveolar rhabdomyosarcoma: Is the cell of origin a mesenchymal stem cell? Cancer Lett. 2009, 279, 126-136.
54. Tirode, F.; Laud-Duval, K.; Prieur, A.; Delorme, B.; Charbord, P.; Delattre, O. Mesenchymal stem cell features of Ewing tumors. Cancer Cell 2007, 11, 421-429.
55. Riggi, N.; Suvà, M.L.; Suvà, D.; Cironi, L.; Provero, P.; Tercier, S.; Joseph, J.M.; Stehle, J.C.; Baumer, K.; Kindler, V.; Stamenkovic, I. EWS-FLI-1 expression triggers a Ewing's sarcoma initiation program in primary human mesenchymal stem cells. Cancer Res. 2008, 68, 2176-2185.
56. Riggi, N.; Suvà, M.L.; De Vito, C.; Provero, P.; Stehle, J.C.; Baumer, K.; Cironi, L.; Janiszewska, M.; Petricevic, T.; Suvà, D.; Tercier, S.; Joseph, J.M.; Guillou, L.; Stamenkovic, I. EWS-FLI-1 modulates miRNA145 and SOX2 expression to initiate mesenchymal stem cell reprogramming toward Ewing sarcoma cancer stem cells. Genes Dev. 2010, 24, 916-932.
57. Friedman, G.K.; Gillespie, G.Y.; Pressey, J.G. Human rhabdomyosarcoma cell lines contain myogenically primitive CD1 33+ cells that are sensitive to killing by engineered herpes simplex virus. 2009 ASPHO Abstracts. Pediatr. Blood and Cancer 2009, 52, 734.
58. Suvà, M.L.; Riggi, N.; Stehle, J.C.; Baumer, K.; Tercier, S.; Joseph, J.M.; Suvà, D.; Clément, V.; Provero, P.; Cironi, L.; Osterheld, M.C.; Guillou, L.; Stamenkovic, I. Identification of cancer stem cells in Ewing's sarcoma. Cancer Res. 2009, 69, 1776-1781.
59. Terry, J.; Nielsen, T. Expression of CD133 in synovial sarcoma. Appl. Immunohistochem. Mol. Morphol. 2010, 18, 159-165.
60. Shmelkov, S.V.; Butler, J.M.; Hooper, A.T.; Hormigo, A.; Kushner, J.; Milde, T.; St Clair, R.; Baljevic, M.; White, I.; Jin, D.K.; Chadburn, A.; Murphy, A.J.; Valenzuela, D.M.; Gale, N.W.; Thurston, G.; Yancopoulos, G.D.; D'Angelica, M.; Kemeny, N.; Lyden, D.; Rafii, S. CD133 expression is not restricted to stem cells, and both CD1 33+ and CD133-metastatic colon cancer cells initiate tumors. J. Clin. Invest. 2008, 118, 2111-2120.
61. Navarro-Alvarez, N.; Kondo, E.; Kawamoto, H.; Hassan, W.; Yuasa, T.; Kubota, Y.; Seita, M.; Nakahara, H.; Hayashi, T.; Nishikawa, Y.; Hassan, R.A., Javed, S.M.; Noguchi, H.; Matsumoto, S.; Nakaji, S.; Tanaka, N.; Kobayashi, N.; Soto-Gutierrez, A. Isolation and Propagation of a Human CD133-Negative Colon Tumor Derived Cell Line with Tumorigenic and Angiogenic Properties. Cell Transplant 2010, 19, 865-877.
62. Meng, X.; Li, M.; Wang, X.; Wang, Y.; Ma, D. Both CD133+ and CD133-subpopulations of A549 and H446 cells contain cancer-initiating cells. Cancer Sci. 2009, 100, 1040-1046.
63. Wang, J.; Sakariassen, P. Ø.; Tsinkalovsky, O.; Immervoll, H.; Bøe, S.O.; Svendsen, A.; Prestegarden, L.; Røsland, G.; Thorsen, F.; Stuhr, L.; Molven, A.; Bjerkvig, R.; Enger, P. Ø. CD133 negative glioma cells form tumors in nude rats and give rise to CD133 positive cells. Int. J. Cancer 2008, 122, 761-768.
64. Ogden, A.T.; Waziri, A.E.; Lochhead, R.A.; Fusco, D.; Lopez, K.; Ellis, J.A.; Kang, J.; Assanah, M.; McKhann, G.M.; Sisti, M.B., McCormick, P.C.; Canoll, P.; Bruce, J.N. Identification of A2B5+CD133-tumor-initiating cells in adult human gliomas. Neurosurgery 2008, 62, 505-514.
65. Srivastava, V.K.; Nalbantoglu, J. Flow cytometric characterization of the DAOY medulloblastoma cell line for the cancer stem-like phenotype. Cytometry A. 2008, 73, 940-948.
66. Griguer, C.E.; Oliva, C.R.; Gobin, E.; Marcorelles, P.; Benos, D.J.; Lancaster, J.R. Jr.; Gillespie, G.Y. CD133 is a marker of bioenergetic stress in human glioma. PLoS One 2008, 3, e3655.
67. Soeda, A.; Park, M.; Lee, D.; Mintz, A.; Androutsellis-Theotokis, A.; McKay, R.D.; Engh, J.; Iwama, T.; Kunisada, T.; Kassam, A.B.; Pollack, I.F.; Park, D.M. Hypoxia promotes expansion of the CD133-positive glioma stem cells through activation of HIF-1alpha. Oncogene 2009, 28, 3949-3959.
68. Kolenda, J.; Jensen, S.S.; Aaberg-Jessen, C.; Christensen, K.; Andersen, C.; Brünner, N.; Kristensen, B.W. Effects of hypoxia on expression of a panel of stem cell and chemoresistance markers in glioblastoma-derived spheroids. J. Neurooncol. 2010, DOI:10.1007/s11060-010-0357-8.
69. Singec, I.; Knoth, R.; Meyer, R.P.; Maciaczyk, J.; Volk, B.; Nikkhah, G.; Frotscher, M.; Snyder, E.Y. Defining the actual sensitivity and specificity of the neurosphere assay in stem cell biology. Nat. Methods 2006, 3, 801-806.
70. Friedman, G.K.; Langford, C.; Coleman, J.; Cassady, K.; Parker, J.; Markert, J.; Gillespie, G.Y. Engineered herpes simplex virus efficiently infects and kills CD133+ glioma cells that express CD1 11. J. Neurooncol. 2009, 95, 199-209.
71. Rich, J.N.; Eyler, C.E. Cancer stem cells in brain tumor biology. Cold Spring Harb. Symp. Quant. Biol. 2008, 73, 411-420.
72. Lathia, J.D.; Gallagher, J.; Heddleston, J.M.; Wang, J.; Eyler, C.E.; Macswords, J.; Wu, Q.; Vasanji, A.; McLendon, R.E.; Hjelmeland, A.B.; Rich, J.N. Integrin alpha 6 regulates glioblastoma stem cells. Cell Stem Cell 2010, 6, 421-432.
73. Hadnagy, A.; Gaboury, L.; Beaulieu, R.; Balicki, D. SP analysis may be used to identify cancer stem cell populations. Exp. Cell Res. 2006, 312, 3701-3710.
74. Komuro, H.; Saihara, R.; Shinya, M.; Takita, J.; Kaneko, S.; Kaneko, M.; Hayashi, Y. Identification of side population cells (stem-like cell population) in pediatric solid tumor cell lines. J. Pediatr. Surg. 2007, 42, 2040-2045.
75. Murase, M.; Kano, M.; Tsukahara, T.; Takahashi, A.; Torigoe, T.; Kawaguchi, S.; Kimura, S.; Wada, T.; Uchihashi, Y.; Kondo, T.; Yamashita, T.; Sato, N. Side population cells have the characteristics of cancer stem-like cells/cancer-initiating cells in bone sarcomas. Br. J. Cancer 2009, 101, 1425-1432.
76. Hayashi, S.; Fujita, K.; Matsumoto, S.; Akita, M.; Satomi, A. Isolation and identification of cancer stem cells from a side population of a human hepatoblastoma cell line, HuH-6 clone-5. Pediatr. Surg. Int. 2011, 27, 9-16.
77. Newton, T.C.; Wolcott, K.; Roberts, S.S. Comparison of the side populations in pretreatment and postrelapse neuroblastoma cell lines. Transl. Oncol. 2010, 3, 246-251.
78. Sneddon, J.B.; Werb, Z. Location, location, location: The cancer stem cell niche. Cell Stem Cell 2007, 1, 607-611.
79. Yang, Z.J.; Wechsler-Reya, R.J. Hit 'em where they live: Targeting the cancer stem cell niche. Cancer Cell 2007, 11, 3-5.
80. Li, L.; Neaves, W.B. Normal stem cells and cancer stem cells: The niche matters. Cancer Res. 2006, 66, 4553-4557.
81. McCawley, L.J.; Matrisian, L.M. Matrix metalloproteinases: Multifunctional contributors to tumor progression. Mol. Med. Today. 2000, 6, 149-156.
82. Kessenbrock, K.; Plaks, V.; Werb, Z. Matrix metalloproteinases: Regulators of the tumor microenvironment. Cell 2010, 141, 52-67.
83. Annabi, B.; Rojas-Sutterlin, S.; Laflamme, C.; Lachambre, M.P.; Rolland, Y.; Sartelet, H.; Béliveau, R. Tumor environment dictates medulloblastoma cancer stem cell expression and invasive phenotype. Mol. Cancer Res. 2008, 6, 907-916.
84. Bao, S.; Wu, Q.; Sathornsumetee, S.; Hao, Y.; Li, Z.; Hjelmeland, A.B.; Shi, Q.; McLendon, R.E.; Bigner, D.D.; Rich, J.N. Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor. Cancer Res. 2006, 66, 7843-7848.
85. Das, B.; Tsuchida, R.; Malkin, D.; Koren, G.; Baruchel, S.; Yeger, H. Hypoxia enhances tumor stemness by increasing the invasive and tumorigenic side population fraction. Stem Cells 2008, 26, 1818-1830.
86. Dahmane, N.; Sánchez. P.; Gitton, Y.; Palma, V.; Sun, T.; Beyna, M.; Weiner, H.; Ruiz, I.; Altaba, A. The Sonic Hedgehog-Gli pathway regulates dorsal brain growth and tumorigenesis. Development 2001, 128, 5201-5212.
87. Pasca di Magliano, M.; Hebrok, M. Hedgehog signalling in cancer formation and maintenance. Nat. Rev. Cancer 2003, 3, 903-911.
88. Artavanis-Tsakonas, S.; Matsuno, K.; Fortini, M.E. Notch signaling. Science 1995, 268, 225-232.
89. Rehman, A.O.; Wang, C.Y. Notch signaling in the regulation of tumor angiogenesis. Trends Cell Biol. 2006, 16, 293-300.
90. van Amerongen, R.; Nusse, R. Towards an integrated view of Wnt signaling in development. Development 2009, 136, 3205-3214.
91. Reya, T.; Clevers, H. Wnt signalling in stem cells and cancer. Nature 2005, 434, 843-850.
92. Zweidler-McKay, P.A. Notch signaling in pediatric malignancies. Curr. Oncol. Rep. 2008, 10, 459-468.
93. Oue, T.; Yoneda, A.; Uehara, S.; Yamanaka, H.; Fukuzawa, M. Increased expression of the hedgehog signaling pathway in pediatric solid malignancies. J. Pediatr. Surg. 2010, 45, 387-392.
94. Moore, S.W. Developmental genes and cancer in children. Pediatr. Blood Cancer 2009, 52, 755-760.
95. Northcott, P.A.; Korshunov, A.; Witt, H.; Hielscher, T.; Eberhart, C.G.; Mack, S.; Bouffet, E.; Clifford, S.C.; Hawkins, C.E.; French, P.; Rutka, J.T.; Pfister, S.; Taylor, M.D. Medulloblastoma Comprises Four Distinct Molecular Variants. J. Clin. Oncol. 2010, DOI:10.1200/JCO.2009.27.4324.
96. Yang, Z.J.; Ellis, T.; Markant, S.L.; Read, T.A.; Kessler, J.D.; Bourboulas, M.; Schüller, U.; Machold, R.; Fishell, G.; Rowitch, D.H.; Wainwright, B.J.; Wechsler-Reya, R.J. Medulloblastoma can be initiated by deletion of Patched in lineage-restricted progenitors or stem cells. Cancer Cell 2008, 14, 135-145.
97. Enguita-Germán, M.; Schiapparelli, P.; Rey, J.A.; Castresana, J.S. CD133+ cells from medulloblastoma and PNET cell lines are more resistant to cyclopamine inhibition of the sonic hedgehog signaling pathway than CD133-cells. Tumour Biol. 2010, 31, 381-390.
98. Fan, X.; Matsui, W.; Khaki, L.; Stearns, D.; Chun, J.; Li, Y.M.; Eberhart, C.G. Notch pathway inhibition depletes stem-like cells and blocks engraftment in embryonal brain tumors. Cancer Res. 2006, 66, 7445-7452.
99. Fujii, H.; Honoki, K.; Tsujiuchi, T.; Kido, A.; Yoshitani, K.; Takakura, Y. Sphere-forming stem-like cell populations with drug resistance in human sarcoma cell lines. Int. J. Oncol. 2009, 34, 1381-1386.
100. Vangipuram, S.D.; Wang, Z.J.; Lyman, W.D. Resistance of stem-like cells from neuroblastoma cell lines to commonly used chemotherapeutic agents. Pediatr. Blood Cancer 2010, 54, 361-368.
101. Jiang, X.; Gwye, Y.; Russell, D.; Cao, C.; Douglas, D.; Hung, L.; Kovar, H.; Triche, T.J.; Lawlor, E.R. CD133 expression in chemo-resistant Ewing sarcoma cells. BMC Cancer 2010, 10, 116.
102. Hussein, D.; Punjaruk, W.; Storer, L.C.; Shaw, L.; Ottoman, R.; Peet, A.; Miller, S.; Bandopadhyay, G.; Heath, R.; Kumari, R.; Bowman, K.J.; Braker, P.; Rahman, R.; Jones, G.D.; Watson, S.; Lowe, J.; Kerr, I.D.; Grundy, R.G.; Coyle, B. Pediatric brain tumor cancer stem cells: Cell cycle dynamics, DNA repair, and etoposide extrusion. Neuro. Oncol. 2011, 13, 70-83.
103. Bao, S.; Wu, Q.; McLendon, R.E.; Hao, Y.; Shi, Q.; Hjelmeland, A.B.; Dewhirst, M.W.; Bigner, D.D.; Rich, J.N. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 2006, 444, 756-760.
104. Yu, C.C.; Chiou, G.Y.; Lee, Y.Y.; Chang, Y.L.; Huang, P.I.; Cheng, Y.W.; Tai, L.K.; Ku, H.H.; Chiou, S.H.; Wong, T.T. Medulloblastoma-derived tumor stem-like cells acquired resistance to TRAIL-induced apoptosis and radiosensitivity. Childs Nerv. Syst. 2010, 26, 897-904.
105. LaBarge, M.A. The difficulty of targeting cancer stem cell niches. Clin. Cancer Res. 2010, 16, 3121-3129.
106. Takebe, N.; Ivy, S.P.; Controversies in cancer stem cells: Targeting embryonic signaling pathways. Clin. Cancer Res. 2010, 16, 3106-3112.
107. Merchant, A.A.; Matsui, W. Targeting Hedgehog--a cancer stem cell pathway. Clin. Cancer Res. 2010, 16, 3130-3140.
108. Pannuti, A.; Foreman, K.; Rizzo, P.; Osipo, C.; Golde, T.; Osborne, B.; Miele, L. Targeting Notch to target cancer stem cells. Clin. Cancer Res. 2010, 16, 3141-3152.
109. Takahashi-Yanaga, F.; Kahn, M. Targeting Wnt signaling: Can we safely eradicate cancer stem cells? Clin. Cancer Res. 2010, 16, 3153-3162.
110. Friedman, G.K.; Pressey, J.G.; Reddy, A.T.; Markert, J.M.; Gillespie, G.Y. Herpes simplex virus oncolytic therapy for pediatric malignancies. Mol. Ther. 2009, 17, 1125-1135.
111. Cripe, T.P.; Wang, P.Y.; Marcato, P.; Mahller, Y.Y.; Lee, P.W. Targeting cancer-initiating cells with oncolytic viruses. Mol. Ther. 2009, 17, 1677-1682.
112. Friedman, G.K.; Bharara, S.; Langford, C.; Coleman, J.; Gillespie, G.Y. Engineered herpes simpex virus oncolytic therapy kills both tumor cells and glioma progenitor cells in a pediatric high-grade glioma. Abstracts from the Thirteenth International Symposium on Pediatric Neuro-Oncology. Neuro. Oncol. 2008, 10, 508-509.