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Journal of Oncology
Volume 2011 (2011), Article ID 549181, 10 pages
http://dx.doi.org/10.1155/2011/549181
Review Article

Lung Cancer Stem Cell: New Insights on Experimental Models and Preclinical Data

Laboratoire UPRES EA 27-10 “Radiosensibilité des Tumeurs et Tissus Sains”, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94800 Villejuif, France

Received 1 October 2010; Accepted 15 November 2010

Academic Editor: Bo Lu

Copyright © 2011 Caroline Rivera 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. T. Reya, S. J. Morrison, M. F. Clarke, and I. L. Weissman, “Stem cells, cancer, and cancer stem cells,” Nature, vol. 414, no. 6859, pp. 105–111, 2001. View at Publisher · View at Google Scholar · View at Scopus
  2. P. C. Nowell, “The clonal evolution of tumor cell populations,” Science, vol. 194, no. 4260, pp. 23–28, 1976. View at Google Scholar · View at Scopus
  3. M. S. Wicha, S. Liu, and G. Dontu, “Cancer stem cells: an old idea—a paradigm shift,” Cancer Research, vol. 66, no. 4, pp. 1883–1890, 2006. View at Publisher · View at Google Scholar · View at Scopus
  4. L. L. Campbell and K. Polyak, “Breast tumor heterogeneity: cancer stem cells or clonal evolution?” Cell Cycle, vol. 6, no. 19, pp. 2332–2338, 2007. View at Google Scholar · View at Scopus
  5. J. E. Visvader and G. J. Lindeman, “Cancer stem cells in solid tumours: accumulating evidence and unresolved questions,” Nature Reviews Cancer, vol. 8, no. 10, pp. 755–768, 2008. View at Publisher · View at Google Scholar · View at Scopus
  6. M. Al-Hajj, M. S. Wicha, A. Benito-Hernandez, S. J. Morrison, and M. F. Clarke, “Prospective identification of tumorigenic breast cancer cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 7, pp. 3983–3988, 2003. View at Publisher · View at Google Scholar · View at Scopus
  7. S. K. Singh, C. Hawkins, I. D. Clarke et al., “Identification of human brain tumour initiating cells,” Nature, vol. 432, no. 7015, pp. 396–401, 2004. View at Publisher · View at Google Scholar · View at Scopus
  8. A. T. Collins and N. J. Maitland, “Prostate cancer stem cells,” European Journal of Cancer, vol. 42, no. 9, pp. 1213–1218, 2006. View at Publisher · View at Google Scholar · View at Scopus
  9. P. C. Hermann, S. L. Huber, T. Herrler et al., “Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer,” Cell Stem Cell, vol. 1, no. 3, pp. 313–323, 2007. View at Publisher · View at Google Scholar · View at Scopus
  10. L. Ricci-Vitiani, D. G. Lombardi, E. Pilozzi et al., “Identification and expansion of human colon-cancer-initiating cells,” Nature, vol. 445, no. 7123, pp. 111–115, 2007. View at Publisher · View at Google Scholar · View at Scopus
  11. A. Eramo, F. Lotti, G. Sette et al., “Identification and expansion of the tumorigenic lung cancer stem cell population,” Cell Death and Differentiation, vol. 15, no. 3, pp. 504–514, 2008. View at Publisher · View at Google Scholar · View at Scopus
  12. C. T. Jordan, M. L. Guzman, and M. Noble, “Cancer stem cells,” The New England Journal of Medicine, vol. 355, no. 12, pp. 1253–1261, 2006. View at Publisher · View at Google Scholar · View at Scopus
  13. N. A. Lobo, Y. Shimono, D. Qian, and M. F. Clarke, “The biology of cancer stem cells,” Annual Review of Cell and Developmental Biology, vol. 23, pp. 675–699, 2007. View at Publisher · View at Google Scholar · View at Scopus
  14. D. T. Scadden, “The stem-cell niche as an entity of action,” Nature, vol. 441, no. 7097, pp. 1075–1079, 2006. View at Publisher · View at Google Scholar · View at Scopus
  15. X. Zhu, X. Zhou, M. T. Lewis, L. Xia, and S. Wong, “Cancer stem cell, niche and EGFR decide tumor development and treatment response: a bio-computational simulation study,” Journal of Theoretical Biology, vol. 269, no. 1, pp. 138–149. View at Publisher · View at Google Scholar
  16. A. E. Cesana and D. M. Noonan, “Cancer stem cells: soloists or choral singers within the tumor micro-environment?” Current Pharmaceutical Biotechnology. Nov 2, 2010. PMID:21044010.
  17. M. F. Clarke and M. Fuller, “Stem cells and cancer: two faces of eve,” Cell, vol. 124, no. 6, pp. 1111–1115, 2006. View at Publisher · View at Google Scholar · View at Scopus
  18. C. Calabrese, H. Poppleton, M. Kocak et al., “A perivascular niche for brain tumor stem cells,” Cancer Cell, vol. 11, no. 1, pp. 69–82, 2007. View at Publisher · View at Google Scholar · View at Scopus
  19. K. Parmar, P. Mauch, J. A. Vergilio, R. Sackstein, and J. D. Down, “Distribution of hematopoietic stem cells in the bone marrow according to regional hypoxia,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 13, pp. 5431–5436, 2007. View at Publisher · View at Google Scholar · View at Scopus
  20. J. Mazumdar, W. T. O'Brien, R. S. Johnson et al., “O2 regulates stem cells through Wnt/β-catenin signalling,” Nature Cell Biology, vol. 12, no. 10, pp. 1007–1013, 2010. View at Publisher · View at Google Scholar
  21. T. Lapidot, C. Sirard, J. Vormoor et al., “A cell initiating human acute myeloid leukaemia after transplantation into SCID mice,” Nature, vol. 367, no. 6464, pp. 645–648, 1994. View at Publisher · View at Google Scholar · View at Scopus
  22. B. A. Reynolds and R. L. Rietze, “Neural stem cells and neurospheres—re-evaluating the relationship,” Nature Methods, vol. 2, no. 5, pp. 333–336, 2005. View at Publisher · View at Google Scholar · View at Scopus
  23. B. G. Debeb, W. Xu, and W. A. Woodward, “Radiation resistance of breast cancer stem cells: understanding the clinical framework,” Journal of Mammary Gland Biology and Neoplasia, vol. 14, no. 1, pp. 11–17, 2009. View at Publisher · View at Google Scholar · View at Scopus
  24. X. Li, M. T. Lewis, J. Huang et al., “Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy,” Journal of the National Cancer Institute, vol. 100, no. 9, pp. 672–679, 2008. View at Publisher · View at Google Scholar · View at Scopus
  25. O. Al-Assar, R. J. Muschel, T. S. Mantoni, W. G. McKenna, and T. B. Brunner, “Radiation response of cancer stem-like cells from established human cell lines after sorting for surface markers,” International Journal of Radiation Oncology Biology Physics, vol. 75, no. 4, pp. 1216–1225, 2009. View at Publisher · View at Google Scholar · View at Scopus
  26. M. Baumann, M. Krause, and R. Hill, “Exploring the role of cancer stem cells in radioresistance,” Nature Reviews Cancer, vol. 8, no. 7, pp. 545–554, 2008. View at Publisher · View at Google Scholar · View at Scopus
  27. M. Zhang, R. L. Atkinson, and J. M. Rosen, “Selective targeting of radiation-resistant tumor-initiating cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 8, pp. 3522–3527, 2010. View at Publisher · View at Google Scholar · View at Scopus
  28. L. P. Martin, T. C. Hamilton, and R. J. Schilder, “Platinum resistance: the role of DNA repair pathways,” Clinical Cancer Research, vol. 14, no. 5, pp. 1291–1295, 2008. View at Publisher · View at Google Scholar · View at Scopus
  29. S. Bao, Q. Wu, R. E. McLendon et al., “Glioma stem cells promote radioresistance by preferential activation of the DNA damage response,” Nature, vol. 444, no. 7120, pp. 756–760, 2006. View at Publisher · View at Google Scholar · View at Scopus
  30. M. A. Goodell, K. Brose, G. Paradis, A. S. Conner, and R. C. Mulligan, “Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo,” Journal of Experimental Medicine, vol. 183, no. 4, pp. 1797–1806, 1996. View at Publisher · View at Google Scholar · View at Scopus
  31. XI. W. Ding, J. H. Wu, and C. P. Jiang, “ABCG2: a potential marker of stem cells and novel target in stem cell and cancer therapy,” Life Sciences, vol. 86, no. 17-18, pp. 631–637, 2010. View at Publisher · View at Google Scholar · View at Scopus
  32. S. Zhou, J. D. Schuetz, K. D. Bunting et al., “The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype,” Nature Medicine, vol. 7, no. 9, pp. 1028–1034, 2001. View at Publisher · View at Google Scholar · View at Scopus
  33. D. H. Ryan, C. W. Chapple, S. A. Kossover, A. S. Sandberg, and H. J. Cohen, “Phenotypic similarities and differences between CALLA-positive acute lymphoblastic leukemia cells and normal marrow CALLA-positive B cell precursors,” Blood, vol. 70, no. 3, pp. 814–821, 1987. View at Google Scholar · View at Scopus
  34. V. Tirino, R. Camerlingo, R. Franco et al., “The role of CD133 in the identification and characterisation of tumour-initiating cells in non-small-cell lung cancer,” European Journal of Cardio-Thoracic Surgery, vol. 36, no. 3, pp. 446–453, 2009. View at Publisher · View at Google Scholar · View at Scopus
  35. Y. Yu, A. Flint, E. L. Dvorin, and J. Bischoff, “AC133-2, a novel isoform of human AC133 stem cell antigen,” Journal of Biological Chemistry, vol. 277, no. 23, pp. 20711–20716, 2002. View at Publisher · View at Google Scholar · View at Scopus
  36. N. Taïeb, M. Maresca, X. J. Guo, N. Garmy, J. Fantini, and N. Yahi, “The first extracellular domain of the tumour stem cell marker CD133 contains an antigenic ganglioside-binding motif,” Cancer Letters, vol. 278, no. 2, pp. 164–173, 2009. View at Publisher · View at Google Scholar · View at Scopus
  37. T. Klonisch, E. Wiechec, S. Hombach-Klonisch et al., “Cancer stem cell markers in common cancers—therapeutic implications,” Trends in Molecular Medicine, vol. 14, no. 10, pp. 450–460, 2008. View at Publisher · View at Google Scholar · View at Scopus
  38. A. Yoshida, A. Rzhetsky, L. C. Hsu, and C. Chang, “Human aldehyde dehydrogenase gene family,” European Journal of Biochemistry, vol. 251, no. 3, pp. 549–557, 1998. View at Google Scholar · View at Scopus
  39. R. J. Jones, J. P. Barber, M. S. Vala et al., “Assessment of aldehyde dehydrogenase in viable cells,” Blood, vol. 85, no. 10, pp. 2742–2746, 1995. View at Google Scholar · View at Scopus
  40. C. Ginestier, M. H. Hur, E. Charafe-Jauffret et al., “ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome,” Cell Stem Cell, vol. 1, no. 5, pp. 555–567, 2007. View at Publisher · View at Google Scholar · View at Scopus
  41. E. H. Huang, M. J. Hynes, T. Zhang et al., “Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis,” Cancer Research, vol. 69, no. 8, pp. 3382–3389, 2009. View at Publisher · View at Google Scholar · View at Scopus
  42. F. Jiang, Q. Qiu, A. Khanna et al., “Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer,” Molecular Cancer Research, vol. 7, no. 3, pp. 330–338, 2009. View at Publisher · View at Google Scholar · View at Scopus
  43. P. N. Kelly, A. Dakic, J. M. Adams, S. L. Nutt, and A. Strasser, “Tumor growth need not be driven by rare cancer stem cells,” Science, vol. 317, no. 5836, p. 337, 2007. View at Publisher · View at Google Scholar · View at Scopus
  44. M. H. Yoo and D. L. Hatfield, “The cancer stem cell theory: is it correct?” Molecules and Cells, vol. 26, no. 5, pp. 514–516, 2008. View at Google Scholar · View at Scopus
  45. K. Rowan, “Are cancer stem cells real? After four decades, debate still simmers,” Journal of the National Cancer Institute, vol. 101, no. 8, pp. 546–547, 2009. View at Publisher · View at Google Scholar · View at Scopus
  46. B. C. Baguley, “Multiple drug resistance mechanisms in cancer,” Molecular Biotechnology, vol. 46, no. 3, pp. 308–316, 2010. View at Publisher · View at Google Scholar
  47. M. V. Berridge, P. M. Herst, and A. S. Tan, “Metabolic flexibility and cell hierarchy in metastatic cancer,” Mitochondrion, vol. 10, no. 6, pp. 584–588, 2010. View at Publisher · View at Google Scholar
  48. J. A. Aguirre-Ghiso, “The problem of cancer dormancy: understanding the basic mechanisms and identifying therapeutic opportunities,” Cell Cycle, vol. 5, no. 16, pp. 1740–1743, 2006. View at Google Scholar · View at Scopus
  49. L. G. Collins, C. Haines, R. Perkel, and R. E. Enck, “Lung cancer: diagnosis and management,” American Family Physician, vol. 75, no. 1, pp. 56–63, 2007. View at Google Scholar · View at Scopus
  50. E. Brambilla, D. Veale, D. Moro, F. Morel, F. Dubois, and C. Brambilla, “Neuroendocrine phenotype in lung cancers: comparison of immunohistochemistry with biochemical determination of enolase isoenzymes,” American Journal of Clinical Pathology, vol. 98, no. 1, pp. 88–97, 1992. View at Google Scholar · View at Scopus
  51. M. Yanada, T. Yaoi, J. Shimada et al., “Frequent hemizygous deletion at 1p36 and hypermethylation downregulate RUNX3 expression in human lung cancer cell lines,” Oncology Reports, vol. 14, no. 4, pp. 817–822, 2005. View at Google Scholar · View at Scopus
  52. K. Hiyama, E. Hiyama, S. Ishioka et al., “Telomerase activity in small-cell and non-small-cell lung cancers,” Journal of the National Cancer Institute, vol. 87, no. 12, pp. 895–902, 1995. View at Google Scholar · View at Scopus
  53. C. I. Amos, W. Xu, and M. R. Spitz, “Is there a genetic basis for lung cancer susceptibility?” Recent Results in Cancer Research, vol. 151, pp. 3–12, 1999. View at Google Scholar · View at Scopus
  54. R. J. Metzger, O. D. Klein, G. R. Martin, and M. A. Krasnow, “The branching programme of mouse lung development,” Nature, vol. 453, no. 7196, pp. 745–750, 2008. View at Publisher · View at Google Scholar · View at Scopus
  55. W. V. Cardoso and J. Lü, “Regulation of early lung morphogenesis: questions, facts and controversies,” Development, vol. 133, no. 9, pp. 1611–1624, 2006. View at Publisher · View at Google Scholar · View at Scopus
  56. M. Weaver, L. Batts, and B. L. M. Hogan, “Tissue interactions pattern the mesenchyme of the embryonic mouse lung,” Developmental Biology, vol. 258, no. 1, pp. 169–184, 2003. View at Publisher · View at Google Scholar · View at Scopus
  57. Y. Ishii, M. Rex, P. J. Scotting, and S. Yasugi, “Region-specific expression of chicken Sox2 in the developing gut and lung epithelium: regulation by epithelial-mesenchymal interactions,” Developmental Dynamics, vol. 213, no. 4, pp. 464–475, 1998. View at Publisher · View at Google Scholar · View at Scopus
  58. C. Gontan, A. de Munck, M. Vermeij, F. Grosveld, D. Tibboel, and R. Rottier, “Sox2 is important for two crucial processes in lung development: branching morphogenesis and epithelial cell differentiation,” Developmental Biology, vol. 317, no. 1, pp. 296–309, 2008. View at Publisher · View at Google Scholar · View at Scopus
  59. T. Okubo, P. S. Knoepfler, R. N. Eisenman, and B. L. M. Hogan, “Nmyc plays an essential role during lung development as a dosage-sensitive regulator of progenitor cell proliferation and differentiation,” Development, vol. 132, no. 6, pp. 1363–1374, 2005. View at Publisher · View at Google Scholar · View at Scopus
  60. A. K. T. Perl, S. E. Wert, A. Nagy, C. G. Lobe, and J. A. Whitsett, “Early restriction of peripheral and proximal cell lineages during formation of the lung,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 16, pp. 10482–10487, 2002. View at Publisher · View at Google Scholar · View at Scopus
  61. R. J. Pack, L. H. Al-Ugaily, G. Morris, and J. G. Widdicombe, “The distribution and structure of cells in the tracheal epithelium of the mouse,” Cell and Tissue Research, vol. 208, no. 1, pp. 65–84, 1980. View at Google Scholar · View at Scopus
  62. K. U. Hong, S. D. Reynolds, S. Watkins, E. Fuchs, and B. R. Stripp, “In vivo differentiation potential of tracheal basal cells: evidence for multipotent and unipotent subpopulations,” American Journal of Physiology, vol. 286, no. 4, pp. L643–L649, 2004. View at Google Scholar · View at Scopus
  63. K. U. Hong, S. D. Reynolds, S. Watkins, E. Fuchs, and B. R. Stripp, “Basal cells are a multipotent progenitor capable of renewing the bronchial epithelium,” American Journal of Pathology, vol. 164, no. 2, pp. 577–588, 2004. View at Google Scholar · View at Scopus
  64. K. Nakanishi, S. Hiroi, T. Kawai, M. Suzuki, and C. Torikata, “Argyrophilic nucleolar-organizer region counts and DNA status in bronchioloalveolar epithelial hyperplasia and adenocarcinoma of the lung,” Human Pathology, vol. 29, no. 3, pp. 235–239, 1998. View at Publisher · View at Google Scholar · View at Scopus
  65. D. Trichopoulos, F. Mollo, L. Tomatis et al., “Active and passive smoking and pathological indicators of lung cancer risk in an autopsy study,” Journal of the American Medical Association, vol. 268, no. 13, pp. 1697–1701, 1992. View at Publisher · View at Google Scholar · View at Scopus
  66. A. Giangreco, E. N. Arwert, I. R. Rosewell, J. Snyder, F. M. Watt, and B. R. Stripp, “Stem cells are dispensable for lung homeostasis but restore airways after injury,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 23, pp. 9286–9291, 2009. View at Publisher · View at Google Scholar · View at Scopus
  67. M. J. Evans, L. J. Cabral Anderson, and G. Freeman, “Role of the clara cell in renewal of the bronchiolar epithelium,” Laboratory Investigation, vol. 38, no. 6, pp. 648–655, 1978. View at Google Scholar · View at Scopus
  68. A. Giangreco, S. D. Reynolds, and B. R. Stripp, “Terminal bronchioles harbor a unique airway stem cell population that localizes to the bronchoalveolar duct junction,” American Journal of Pathology, vol. 161, no. 1, pp. 173–182, 2002. View at Google Scholar · View at Scopus
  69. S. D. Reynolds, A. Giangreco, J. H. T. Power, and B. R. Stripp, “Neuroepithelial bodies of pulmonary airways serve as a reservoir of progenitor cells capable of epithelial regeneration,” American Journal of Pathology, vol. 156, no. 1, pp. 269–278, 2000. View at Google Scholar · View at Scopus
  70. T. P. Stevens, J. T. Mcbride, J. L. Peake, K. E. Pinkerton, and B. R. Stripp, “Cell proliferation contributes to PNEC hyperplasia after acute airway injury,” American Journal of Physiology, vol. 272, no. 3, pp. L486–L493, 1997. View at Google Scholar · View at Scopus
  71. R. I. Linnoila, S. M. Jensen, S. M. Steinberg, J. L. Mulshine, J. C. Eggleston, and A. F. Gazdar, “Peripheral airway cell marker expression in non-small cell lung carcinoma. Association with distinct clinicopathologic features,” American Journal of Clinical Pathology, vol. 97, no. 2, pp. 233–243, 1992. View at Google Scholar · View at Scopus
  72. L. M. Eisenberg and C. A. Eisenberg, “Stem cell plasticity, cell fusion, and transdifferentiation,” Birth Defects Research Part C, vol. 69, no. 3, pp. 209–218, 2003. View at Publisher · View at Google Scholar · View at Scopus
  73. S. J. Forbes, P. Vig, R. Poulsom, N. A. Wright, and M. R. Alison, “Adult stem cell plasticity: new pathways of tissue regeneration become visible,” Clinical Science, vol. 103, no. 4, pp. 355–369, 2002. View at Google Scholar · View at Scopus
  74. C. F. Kim, E. L. Jackson, A. E. Woolfenden et al., “Identification of bronchioalveolar stem cells in normal lung and lung cancer,” Cell, vol. 121, no. 6, pp. 823–835, 2005. View at Publisher · View at Google Scholar · View at Scopus
  75. N. Onuki, I. I. Wistuba, W. D. Travis et al., “Genetic changes in the spectrum of neuroendocrine lung tumors,” Cancer, vol. 85, no. 3, pp. 600–607, 1999. View at Publisher · View at Google Scholar · View at Scopus
  76. R. Meuwissen and A. Berns, “Mouse models for human lung cancer,” Genes and Development, vol. 19, no. 6, pp. 643–664, 2005. View at Publisher · View at Google Scholar · View at Scopus
  77. N. Ohtsuka, K. Urase, T. Momoi, and H. Nogawa, “Induction of bud formation of embryonic mouse tracheal epithelium by fibroblast growth factor plus transferrin in mesenchyme-free culture,” Developmental Dynamics, vol. 222, no. 2, pp. 263–272, 2001. View at Publisher · View at Google Scholar · View at Scopus
  78. A. Giangreco, K. R. Groot, and S. M. Janes, “Lung cancer and lung stem cells: strange bedfellows?” American Journal of Respiratory and Critical Care Medicine, vol. 175, no. 6, pp. 547–553, 2007. View at Publisher · View at Google Scholar · View at Scopus
  79. L. Li and W. B. Neaves, “Normal stem cells and cancer stem cells: the niche matters,” Cancer Research, vol. 66, no. 9, pp. 4553–4557, 2006. View at Publisher · View at Google Scholar · View at Scopus
  80. M. M. Ho, A. V. Ng, S. Lam, and J. Y. Hung, “Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells,” Cancer Research, vol. 67, no. 10, pp. 4827–4833, 2007. View at Publisher · View at Google Scholar · View at Scopus
  81. R. Summer, D. N. Kotton, X. Sun, B. Ma, K. Fitzsimmons, and A. Fine, “Side population cells and Bcrp1 expression in lung,” American Journal of Physiology, vol. 285, no. 1, pp. L97–L104, 2003. View at Google Scholar · View at Scopus
  82. J. M. Sung, H. J. Cho, H. Yi et al., “Characterization of a stem cell population in lung cancer A549 cells,” Biochemical and Biophysical Research Communications, vol. 371, no. 1, pp. 163–167, 2008. View at Publisher · View at Google Scholar · View at Scopus
  83. C. D. Salcido, A. Larochelle, B. J. Taylor, C. E. Dunbar, and L. Varticovski, “Molecular characterisation of side population cells with cancer stem cell-like characteristics in small-cell lung cancer,” British Journal of Cancer, vol. 102, no. 11, pp. 1636–1644, 2010. View at Publisher · View at Google Scholar · View at Scopus
  84. A. Eramo, T. L. Haas, and R. De Maria, “Lung cancer stem cells: tools and targets to fight lung cancer,” Oncogene, 2010. View at Publisher · View at Google Scholar · View at Scopus
  85. S. Deng, X. Yang, H. Lassus et al., “Distinct expression levels and patterns of stem cell marker, aldehyde dehydrogenase isoform 1 (ALDH1), in human epithelial cancers,” PLoS One, vol. 5, no. 4, Article ID e10277, 2010. View at Publisher · View at Google Scholar
  86. V. Levina, A. M. Marrangoni, R. DeMarco, E. Gorelik, and A. E. Lokshin, “Drug-selected human lung cancer stem cells: cytokine network, tumorigenic and metastatic properties,” PLoS One, vol. 3, no. 8, Article ID e3077, 2008. View at Publisher · View at Google Scholar · View at Scopus
  87. Y. C. Chen, H. S. Hsu, Y. W. Chen et al., “Oct-4 expression maintained cancer stem-like properties in lung cancer-derived CD133-positive cells,” PLoS One, vol. 3, no. 7, Article ID e2637, 2008. View at Publisher · View at Google Scholar · View at Scopus
  88. G. Bertolini, L. Roz, P. Perego et al., “Highly tumorigenic lung cancer CD133 cells display stem-like features and are spared by cisplatin treatment,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 38, pp. 16281–16286, 2009. View at Publisher · View at Google Scholar · View at Scopus
  89. V. Tirino, V. Desiderio, R. D'Aquino et al., “Detection and characterization of CD133 cancer stem cells in human solid tumours,” PLoS One, vol. 3, no. 10, Article ID e3469, 2008. View at Publisher · View at Google Scholar · View at Scopus
  90. A. V. Salnikov, J. Gladkich, G. Moldenhauer, M. Volm, J. Mattern, and I. Herr, “CD133 is indicative for a resistance phenotype but does not represent a prognostic marker for survival of non-small cell lung cancer patients,” International Journal of Cancer, vol. 126, no. 4, pp. 950–958, 2010. View at Publisher · View at Google Scholar · View at Scopus
  91. F. Li, H. Zeng, and K. Ying, “The combination of stem cell markers CD133 and ABCG2 predicts relapse in stage I non-small cell lung carcinomas,” Medical Oncology. Aug 18, 2010. PMID:20717756. View at Publisher · View at Google Scholar
  92. T. Bonnefoix, P. Bonnefoix, P. Verdiel, and J. J. Sotto, “Fitting limiting dilution experiments with generalized linear models results in a test of the single-hit Poisson assumption,” Journal of Immunological Methods, vol. 194, no. 2, pp. 113–119, 1996. View at Publisher · View at Google Scholar · View at Scopus
  93. E. L. Jackson, N. Willis, K. Mercer et al., “Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras,” Genes and Development, vol. 15, no. 24, pp. 3243–3248, 2001. View at Publisher · View at Google Scholar · View at Scopus
  94. J. M. Bishop, “The molecular genetics of cancer,” Science, vol. 235, no. 4786, pp. 305–311, 1987. View at Google Scholar · View at Scopus
  95. E. R. Cameron and J. C. Neil, “The Runx genes: lineage-specific oncogenes and tumor suppressors,” Oncogene, vol. 23, no. 24, pp. 4308–4314, 2004. View at Publisher · View at Google Scholar · View at Scopus
  96. C. G. de Guzman, A. J. Warren, Z. Zhang et al., “Hematopoietic stem cell expansion and distinct myeloid developmental abnormalities in a murine model of the AML1-ETO translocation,” Molecular and Cellular Biology, vol. 22, no. 15, pp. 5506–5517, 2002. View at Publisher · View at Google Scholar · View at Scopus
  97. K. S. Lee, Y. S. Lee, J. M. Lee et al., “Runx3 is required for the differentiation of lung epithelial cells and suppression of lung cancer,” Oncogene, vol. 29, no. 23, pp. 3349–3361, 2010. View at Publisher · View at Google Scholar · View at Scopus
  98. Q. L. Li, H. R. Kim, W. J. Kim et al., “Transcriptional silencing of the RUNX3 gene by CpG hypermethylation is associated with lung cancer,” Biochemical and Biophysical Research Communications, vol. 314, no. 1, pp. 223–228, 2004. View at Publisher · View at Google Scholar · View at Scopus
  99. J. D. F. Licchesi, W. H. Westra, C. M. Hooker, E. O. Machida, S. B. Baylin, and J. G. Herman, “Epigenetic alteration of wnt pathway antagonists in progressive glandular neoplasia of the lung,” Carcinogenesis, vol. 29, no. 5, pp. 895–904, 2008. View at Publisher · View at Google Scholar · View at Scopus
  100. K. A. Kwei, Y. H. Kim, L. Girard et al., “Genomic profiling identifies TITF1 as a lineage-specific oncogene amplified in lung cancer,” Oncogene, vol. 27, no. 25, pp. 3635–3640, 2008. View at Publisher · View at Google Scholar · View at Scopus
  101. W. W. Lockwood, R. Chari, B. P. Coe et al., “Integrative genomic analyses identify BRF2 as a novel lineage-specific oncogene in lung squamous cell carcinoma,” PLoS Medicine, vol. 7, no. 7, Article ID e1000315, 2010. View at Publisher · View at Google Scholar
  102. X. Zhang, B. Han, J. Huang et al., “Prognostic significance of OCT4 expression in adenocarcinoma of the lung,” Japanese Journal of Clinical Oncology, vol. 40, no. 10, pp. 961–966, 2010. View at Publisher · View at Google Scholar
  103. G. Karoubi, M. Gugger, R. Schmid, and A. Dutly, “OCT4 expression in human non-small cell lung cancer: implications for therapeutic intervention,” Interactive Cardiovascular and Thoracic Surgery, vol. 8, no. 4, p. 397, 2009. View at Publisher · View at Google Scholar · View at Scopus
  104. T. Hu, S. Liu, D. R. Breiter, F. Wang, Y. Tang, and S. Sun, “Octamer 4 small interfering RNA results in cancer stem cell-like cell apoptosis,” Cancer Research, vol. 68, no. 16, pp. 6533–6540, 2008. View at Publisher · View at Google Scholar · View at Scopus
  105. L. A. Boyer, I. L. Tong, M. F. Cole et al., “Core transcriptional regulatory circuitry in human embryonic stem cells,” Cell, vol. 122, no. 6, pp. 947–956, 2005. View at Publisher · View at Google Scholar · View at Scopus
  106. N. Ivanova, R. Dobrin, R. Lu et al., “Dissecting self-renewal in stem cells with RNA interference,” Nature, vol. 442, no. 7102, pp. 533–538, 2006. View at Publisher · View at Google Scholar · View at Scopus
  107. T. Hussenet, S. Dali, J. Exinger et al., “SOX2 is an oncogene activated by recurrent 3q26.3 amplifications in human lung squamous cell carcinomas,” PLoS One, vol. 5, Article ID e8960, 15 pages, 2010. View at Publisher · View at Google Scholar · View at Scopus
  108. Y. Lu, C. Futtner, J. R. Rock et al., “Evidence that SOX2 overexpression is oncogenic in the lung,” PLoS One, vol. 5, no. 6, Article ID e11022, 2010. View at Publisher · View at Google Scholar
  109. K. Takahashi and S. Yamanaka, “Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors,” Cell, vol. 126, no. 4, pp. 663–676, 2006. View at Publisher · View at Google Scholar · View at Scopus
  110. M. Wernig, A. Meissner, R. Foreman et al., “In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state,” Nature, vol. 448, no. 7151, pp. 318–324, 2007. View at Publisher · View at Google Scholar · View at Scopus
  111. G. W. Krystal, S. J. Hines, and C. P. Organ, “Autocrine growth of small cell lung cancer mediated by coexpression of c-kit and stem cell factor,” Cancer Research, vol. 56, no. 2, pp. 370–376, 1996. View at Google Scholar · View at Scopus
  112. S. J. Hines, C. Organ, M. J. Kornstein, and G. W. Krystal, “Coexpression of the c-kit and stem cell factor genes in breast carcinomas,” Cell Growth and Differentiation, vol. 6, no. 6, pp. 769–779, 1995. View at Google Scholar · View at Scopus
  113. A. Yasuda, H. Sawai, H. Takahashi et al., “Stem cell factor/c-kit receptor signaling enhances the proliferation and invasion of colorectal cancer cells through the PI3K/Akt Pathway,” Digestive Diseases and Sciences, vol. 52, no. 9, pp. 2292–2300, 2007. View at Publisher · View at Google Scholar
  114. H. T. Hassan, “c-Kit expression in human normal and malignant stem cells prognostic and therapeutic implications,” Leukemia Research, vol. 33, no. 1, pp. 5–10, 2009. View at Publisher · View at Google Scholar · View at Scopus
  115. V. Levina, A. Marrangoni, T. Wang et al., “Elimination of human lung cancer stem cells through targeting of the stem cell factor-c-kit autocrine signaling loop,” Cancer Research, vol. 70, no. 1, pp. 338–346, 2010. View at Publisher · View at Google Scholar