Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Lung cancer stem cells: tools and targets to fight lung cancer

Oncogene volume 29, pages 4625–4635 (2010)Cite this article

Subjects

Abstract

Cancer stem cell (CSC) theory states that tumors are organized in a similar hierarchical manner as normal tissues, with a sub-population of tumorigenic stem-like cells that generate the more differentiated nontumorigenic tumor cells. CSCs are chemoresistant and seem to be responsible for tumor recurrence and formation of metastases. Therefore, the study of these cells may lead to crucial advances in the understanding of tumor biology as well as to innovative and more effective therapies. Lung cancer represents the leading cause of cancer-related mortality worldwide. Despite improvements in medical and surgical management, patient survival rates remain stable at ∼15%, calling for innovative strategies that may contribute to improve patient outcome. The discovery of lung CSCs and the possibility to characterize their biological properties may provide powerful translational tools to improve the clinical outcome of patients with lung cancer. In this report, we review what is known about lung CSCs and discuss the diagnostic, prognostic and therapeutic prospective of these findings.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  • Aktas B, Tewes M, Fehm T, Hauch S, Kimmig R, Kasimir-Bauer S . (2009). Stem cell and epithelial-mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients. Breast Cancer Res 11: R46.

    Google Scholar 

  • Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF . (2003). Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100: 3983–3988.

    Article  CAS  Google Scholar 

  • Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB et al. (2006). Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444: 756–760.

    Article  CAS  Google Scholar 

  • Barker N, Ridgway RA, van Es JH, van de Wetering M, Begthel H, van den Born M et al. (2009). Crypt stem cells as the cells-of-origin of intestinal cancer. Nature 457: 608–611.

    Article  CAS  Google Scholar 

  • Barker N, van de Wetering M, Clevers H . (2008). The intestinal stem cell. Genes Dev 22: 1856–1864.

    CAS  Google Scholar 

  • Beier D, Hau P, Proescholdt M, Lohmeier A, Wischhusen J, Oefner PJ et al. (2007). CD133(+) and CD133(−) glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles. Cancer Res 67: 4010–4015.

    Article  CAS  Google Scholar 

  • Bertolini G, Roz L, Perego P, Tortoreto M, Fontanella E, Gatti L et al. (2009). Highly tumorigenic lung cancer CD133+ cells display stem-like features and are spared by cisplatin treatment. Proc Natl Acad Sci USA 106: 16281–16286.

    CAS  Google Scholar 

  • Besson A, Hwang HC, Cicero S, Donovan SL, Gurian-West M, Johnson D et al. (2007). Discovery of an oncogenic activity in p27Kip1 that causes stem cell expansion and a multiple tumor phenotype. Genes Dev 21: 1731–1746.

    CAS  Google Scholar 

  • Bhattacharjee A, Richards WG, Staunton J, Li C, Monti S, Vasa P et al. (2001). Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. Proc Natl Acad Sci USA 98: 13790–13795.

    CAS  Google Scholar 

  • Bianchi F, Nicassio F, Di Fiore PP . (2008). Unbiased vs biased approaches to the identification of cancer signatures: the case of lung cancer. Cell Cycle 7: 729–734.

    CAS  Google Scholar 

  • Blau HM, Brazelton TR, Weimann JM . (2001). The evolving concept of a stem cell: entity or function? Cell 105: 829–841.

    CAS  Google Scholar 

  • Blenkinsopp WK . (1967). Proliferation of respiratory tract epithelium in the rat. Exp Cell Res 46: 144–154.

    CAS  Google Scholar 

  • Bonnet D, Dick JE . (1997). Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3: 730–737.

    CAS  Google Scholar 

  • Borczuk AC, Toonkel RL, Powell CA . (2009). Genomics of lung cancer. Proc Am Thorac Soc 6: 152–158.

    CAS  Google Scholar 

  • Calabrese C, Poppleton H, Kocak M, Hogg TL, Fuller C, Hamner B et al. (2007). A perivascular niche for brain tumor stem cells. Cancer Cell 11: 69–82.

    CAS  Google Scholar 

  • Chen Y, Chan VS, Zheng B, Chan KY, Xu X, To LY et al. (2007). A novel subset of putative stem/progenitor CD34+Oct-4+ cells is the major target for SARS coronavirus in human lung. J Exp Med 204: 2529–2536.

    CAS  Google Scholar 

  • Chen YC, Hsu HS, Chen YW, Tsai TH, How CK, Wang CY et al. (2008). Oct-4 expression maintained cancer stem-like properties in lung cancer-derived CD133-positive cells. PLoS One 3: e2637.

    Google Scholar 

  • Cicalese A, Bonizzi G, Pasi CE, Faretta M, Ronzoni S, Giulini B et al. (2009). The tumor suppressor p53 regulates polarity of self-renewing divisions in mammary stem cells. Cell 138: 1083–1095.

    CAS  Google Scholar 

  • Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL et al. (2006). Cancer stem cells—perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res 66: 9339–9344.

    CAS  Google Scholar 

  • Collins LG, Haines C, Perkel R, Enck RE . (2007). Lung cancer: diagnosis and management. Am Fam Physician 75: 56–63.

    Google Scholar 

  • Creighton CJ, Li X, Landis M, Dixon JM, Neumeister VM, Sjolund A et al. (2009). Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proc Natl Acad Sci USA 106: 13820–13825.

    CAS  Google Scholar 

  • Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW et al. (2007). Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA 104: 10158–10163.

    CAS  Google Scholar 

  • Dubey S, Powell CA . (2008). Update in lung cancer 2007. Am J Respir Crit Care Med 177: 941–946.

    CAS  Google Scholar 

  • Dubey S, Powell CA . (2009). Update in lung cancer 2008. Am J Respir Crit Care Med 179: 860–868.

    CAS  Google Scholar 

  • Dylla SJ, Beviglia L, Park IK, Chartier C, Raval J, Ngan L et al. (2008). Colorectal cancer stem cells are enriched in xenogeneic tumors following chemotherapy. PLoS One 3: e2428.

    Google Scholar 

  • Eramo A, Lotti F, Sette G, Pilozzi E, Biffoni M, Di Virgilio A et al. (2008). Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ 15: 504–514.

    CAS  Google Scholar 

  • Fuchs E . (2009). The tortoise and the hair: slow-cycling cells in the stem cell race. Cell 137: 811–819.

    CAS  Google Scholar 

  • Giangreco A, Arwert EN, Rosewell IR, Snyder J, Watt FM, Stripp BR . (2009). Stem cells are dispensable for lung homeostasis but restore airways after injury. Proc Natl Acad Sci USA 106: 9286–9291.

    CAS  Google Scholar 

  • Giangreco A, Groot KR, Janes SM . (2007). Lung cancer and lung stem cells: strange bedfellows? Am J Respir Crit Care Med 175: 547–553.

    Google Scholar 

  • Giangreco A, Reynolds SD, Stripp BR . (2002). Terminal bronchioles harbor a unique airway stem cell population that localizes to the bronchoalveolar duct junction. Am J Pathol 161: 173–182.

    Google Scholar 

  • Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M et al. (2007). ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1: 555–567.

    CAS  Google Scholar 

  • Guan Y, Gerhard B, Hogge DE . (2003). Detection, isolation, and stimulation of quiescent primitive leukemic progenitor cells from patients with acute myeloid leukemia (AML). Blood 101: 3142–3149.

    CAS  Google Scholar 

  • Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA et al. (2009). Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell 138: 645–659.

    CAS  Google Scholar 

  • Hill RP . (2006). Identifying cancer stem cells in solid tumors: case not proven. Cancer Res 66: 1891–1895.

    CAS  Google Scholar 

  • Ho MM, Ng AV, Lam S, Hung JY . (2007). Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells. Cancer Res 67: 4827–4833.

    CAS  Google Scholar 

  • Holyoake T, Jiang X, Eaves C, Eaves A . (1999). Isolation of a highly quiescent subpopulation of primitive leukemic cells in chronic myeloid leukemia. Blood 94: 2056–2064.

    CAS  Google Scholar 

  • Hong KU, Reynolds SD, Watkins S, Fuchs E, Stripp BR . (2004a). Basal cells are a multipotent progenitor capable of renewing the bronchial epithelium. Am J Pathol 164: 577–588.

    CAS  Google Scholar 

  • Hong KU, Reynolds SD, Watkins S, Fuchs E, Stripp BR . (2004b). in vivo differentiation potential of tracheal basal cells: evidence for multipotent and unipotent subpopulations. Am J Physiol Lung Cell Mol Physiol 286: L643–L649.

    CAS  Google Scholar 

  • Hu T, Liu S, Breiter DR, Wang F, Tang Y, Sun S . (2008). Octamer 4 small interfering RNA results in cancer stem cell-like cell apoptosis. Cancer Res 68: 6533–6540.

    CAS  Google Scholar 

  • Huang EH, Hynes MJ, Zhang T, Ginestier C, Dontu G, Appelman H et al. (2009). Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis. Cancer Res 69: 3382–3389.

    CAS  Google Scholar 

  • Ishikawa F, Yoshida S, Saito Y, Hijikata A, Kitamura H, Tanaka S et al. (2007). Chemotherapy-resistant human AML stem cells home to and engraft within the bone-marrow endosteal region. Nat Biotechnol 25: 1315–1321.

    CAS  Google Scholar 

  • Iwasaki H, Akashi K . (2007). Myeloid lineage commitment from the hematopoietic stem cell. Immunity 26: 726–740.

    CAS  Google Scholar 

  • Jackson EL, Willis N, Mercer K, Bronson RT, Crowley D, Montoya R et al. (2001). Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras. Genes Dev 15: 3243–3248.

    CAS  Google Scholar 

  • Janne PA, Engelman JA, Johnson BE . (2005). Epidermal growth factor receptor mutations in non-small-cell lung cancer: implications for treatment and tumor biology. J Clin Oncol 23: 3227–3234.

    CAS  Google Scholar 

  • Jemal A, Thun MJ, Ries LA, Howe HL, Weir HK, Center MM et al. (2008). Annual report to the nation on the status of cancer, 1975–2005, featuring trends in lung cancer, tobacco use, and tobacco control. J Natl Cancer Inst 100: 1672–1694.

    Google Scholar 

  • Jiang F, Qiu Q, Khanna A, Todd NW, Deepak J, Xing L et al. (2009). Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer. Mol Cancer Res 7: 330–338.

    CAS  Google Scholar 

  • Jin L, Hope KJ, Zhai Q, Smadja-Joffe F, Dick JE . (2006). Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat Med 12: 1167–1174.

    Article  Google Scholar 

  • Jin L, Lee EM, Ramshaw HS, Busfield SJ, Peoppl AG, Wilkinson L et al. (2009). Monoclonal antibody-mediated targeting of CD123, IL-3 receptor alpha chain, eliminates human acute myeloid leukemic stem cells. Cell Stem Cell 5: 31–42.

    CAS  Google Scholar 

  • Kim CF, Jackson EL, Woolfenden AE, Lawrence S, Babar I, Vogel S et al. (2005). Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 121: 823–835.

    CAS  Google Scholar 

  • Kuperwasser C, Chavarria T, Wu M, Magrane G, Gray JW, Carey L et al. (2004). Reconstruction of functionally normal and malignant human breast tissues in mice. Proc Natl Acad Sci USA 101: 4966–4971.

    CAS  Google Scholar 

  • Lantuejoul S, Salameire D, Salon C, Brambilla E . (2009). Pulmonary preneoplasia—sequential molecular carcinogenetic events. Histopathology 54: 43–54.

    Google Scholar 

  • Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J et al. (1994). A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367: 645–648.

    CAS  Google Scholar 

  • Lee A, Kessler JD, Read TA, Kaiser C, Corbeil D, Huttner WB et al. (2005). Isolation of neural stem cells from the postnatal cerebellum. Nat Neurosci 8: 723–729.

    CAS  Google Scholar 

  • Levina V, Marrangoni AM, DeMarco R, Gorelik E, Lokshin AE . (2008). Drug-selected human lung cancer stem cells: cytokine network, tumorigenic and metastatic properties. PLoS One 3: e3077.

    Google Scholar 

  • Li X, Lewis MT, Huang J, Gutierrez C, Osborne CK, Wu MF et al. (2008). Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J Natl Cancer Inst 100: 672–679.

    CAS  Google Scholar 

  • Ling TY, Kuo MD, Li CL, Yu AL, Huang YH, Wu TJ et al. (2006). Identification of pulmonary Oct-4+ stem/progenitor cells and demonstration of their susceptibility to SARS coronavirus (SARS-CoV) infection in vitro. Proc Natl Acad Sci USA 103: 9530–9535.

    CAS  Google Scholar 

  • Maeda S, Shinchi H, Kurahara H, Mataki Y, Maemura K, Sato M et al. (2008). CD133 expression is correlated with lymph node metastasis and vascular endothelial growth factor-C expression in pancreatic cancer. Br J Cancer 98: 1389–1397.

    CAS  Google Scholar 

  • Mahvi D, Bank H, Harley R . (1977). Morphology of a naphthalene-induced bronchiolar lesion. Am J Pathol 86: 558–572.

    CAS  Google Scholar 

  • Minna JD, Roth JA, Gazdar AF . (2002). Focus on lung cancer. Cancer Cell 1: 49–52.

    CAS  Google Scholar 

  • O'Brien CA, Pollett A, Gallinger S, Dick JE . (2007). A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445: 106–110.

    CAS  Google Scholar 

  • Orkin SH, Zon LI . (2002). Hematopoiesis and stem cells: plasticity versus developmental heterogeneity. Nat Immunol 3: 323–328.

    CAS  Google Scholar 

  • Pallini R, Ricci-Vitiani L, Banna GL, Signore M, Lombardi D, Todaro M et al. (2008). Cancer stem cell analysis and clinical outcome in patients with glioblastoma multiforme. Clin Cancer Res 14: 8205–8212.

    CAS  Google Scholar 

  • Pantel K, Alix-Panabieres C, Riethdorf S . (2009). Cancer micrometastases. Nat Rev Clin Oncol 6: 339–351.

    CAS  Google Scholar 

  • Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I et al. (2004). EGF receptor gene mutations are common in lung cancers from ‘never smokers’ and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci USA 101: 13306–13311.

    CAS  Google Scholar 

  • Pao W, Wang TY, Riely GJ, Miller VA, Pan Q, Ladanyi M et al. (2005). KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med 2: e17.

    Google Scholar 

  • Pece S, Tosoni D, Confalonieri S, Mazzarol G, Vecchi M, Ronzoni S et al. (2010). Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content. Cell 140: 62–73.

    CAS  Google Scholar 

  • Piccirillo SG, Reynolds BA, Zanetti N, Lamorte G, Binda E, Broggi G et al. (2006). Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells. Nature 444: 761–765.

    CAS  Google Scholar 

  • Pollard SM, Yoshikawa K, Clarke ID, Danovi D, Stricker S, Russell R et al. (2009). Glioma stem cell lines expanded in adherent culture have tumor-specific phenotypes and are suitable for chemical and genetic screens. Cell Stem Cell 4: 568–580.

    CAS  Google Scholar 

  • Rawlins EL . (2008). Lung epithelial progenitor cells: lessons from development. Proc Am Thorac Soc 5: 675–681.

    Google Scholar 

  • Rawlins EL, Okubo T, Xue Y, Brass DM, Auten RL, Hasegawa H et al. (2009). The role of Scgb1a1+ Clara cells in the long-term maintenance and repair of lung airway, but not alveolar, epithelium. Cell Stem Cell 4: 525–534.

    CAS  Google Scholar 

  • Reya T, Morrison SJ, Clarke MF, Weissman IL . (2001). Stem cells, cancer, and cancer stem cells. Nature 414: 105–111.

    CAS  Google Scholar 

  • Reynolds BA, Weiss S . (1992). Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255: 1707–1710.

    CAS  Google Scholar 

  • Reynolds SD, Giangreco A, Power JH, Stripp BR . (2000). Neuroepithelial bodies of pulmonary airways serve as a reservoir of progenitor cells capable of epithelial regeneration. Am J Pathol 156: 269–278.

    CAS  Google Scholar 

  • Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C et al. (2007). Identification and expansion of human colon-cancer-initiating cells. Nature 445: 111–115.

    CAS  Google Scholar 

  • Riely GJ, Marks J, Pao W . (2009). KRAS mutations in non-small cell lung cancer. Proc Am Thorac Soc 6: 201–205.

    CAS  Google Scholar 

  • Ross JS, Slodkowska EA . (2009). Circulating and disseminated tumor cells in the management of breast cancer. Am J Clin Pathol 132: 237–245.

    CAS  Google Scholar 

  • Scagliotti G, Hanna N, Fossella F, Sugarman K, Blatter J, Peterson P et al. (2009). The differential efficacy of pemetrexed according to NSCLC histology: a review of two phase III studies. Oncologist 14: 253–263.

    CAS  Google Scholar 

  • Schatton T, Frank NY, Frank MH . (2009). Identification and targeting of cancer stem cells. Bioessays 31: 1038–1049.

    CAS  Google Scholar 

  • Sekido Y, Fong KM, Minna JD . (2003). Molecular genetics of lung cancer. Annu Rev Med 54: 73–87.

    CAS  Google Scholar 

  • Sholl LM, Long KB, Hornick JL . (2009). Sox2 expression in pulmonary non-small cell and neuroendocrine carcinomas. Appl Immunohistochem Mol Morphol 18: 55–61.

    Google Scholar 

  • Shultz LD, Lyons BL, Burzenski LM, Gott B, Chen X, Chaleff S et al. (2005). Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells. J Immunol 174: 6477–6489.

    CAS  Google Scholar 

  • Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J et al. (2003). Identification of a cancer stem cell in human brain tumors. Cancer Res 63: 5821–5828.

    CAS  Google Scholar 

  • Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T et al. (2004). Identification of human brain tumour initiating cells. Nature 432: 396–401.

    CAS  Google Scholar 

  • Song W, Li H, Tao K, Li R, Song Z, Zhao Q et al. (2008). Expression and clinical significance of the stem cell marker CD133 in hepatocellular carcinoma. Int J Clin Pract 62: 1212–1218.

    CAS  Google Scholar 

  • Storms RW, Trujillo AP, Springer JB, Shah L, Colvin OM, Ludeman SM et al. (1999). Isolation of primitive human hematopoietic progenitors on the basis of aldehyde dehydrogenase activity. Proc Natl Acad Sci USA 96: 9118–9123.

    CAS  Google Scholar 

  • Stripp BR, Maxson K, Mera R, Singh G . (1995). Plasticity of airway cell proliferation and gene expression after acute naphthalene injury. Am J Physiol 269: L791–L799.

    CAS  Google Scholar 

  • Stripp BR, Reynolds SD . (2008). Maintenance and repair of the bronchiolar epithelium. Proc Am Thorac Soc 5: 328–333.

    Google Scholar 

  • Theodoropoulos PA, Polioudaki H, Agelaki S, Kallergi G, Saridaki Z, Mavroudis D et al. (2009). Circulating tumor cells with a putative stem cell phenotype in peripheral blood of patients with breast cancer. Cancer Lett. 288: 99–106.

    Google Scholar 

  • Tiseo M, Bartolotti M, Gelsomino F, Ardizzoni A . (2009). First-line treatment in advanced non-small-cell lung cancer: the emerging role of the histologic subtype. Expert Rev Anticancer Ther 9: 425–435.

    CAS  Google Scholar 

  • Todaro M, Alea MP, Di Stefano AB, Cammareri P, Vermeulen L, Iovino F et al. (2007). Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4. Cell Stem Cell 1: 389–402.

    CAS  Google Scholar 

  • Todaro M, Perez Alea M, Scopelliti A, Medema JP, Stassi G . (2008). IL-4-mediated drug resistance in colon cancer stem cells. Cell Cycle 7: 309–313.

    CAS  Google Scholar 

  • Van Winkle LS, Buckpitt AR, Nishio SJ, Isaac JM, Plopper CG . (1995). Cellular response in naphthalene-induced Clara cell injury and bronchiolar epithelial repair in mice. Am J Physiol 269: L800–L818.

    CAS  Google Scholar 

  • Ventura JJ, Tenbaum S, Perdiguero E, Huth M, Guerra C, Barbacid M et al. (2007). p38alpha MAP kinase is essential in lung stem and progenitor cell proliferation and differentiation. Nat Genet 39: 750–758.

    CAS  Google Scholar 

  • Visvader JE, Lindeman GJ . (2008). Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer 8: 755–768.

    CAS  Google Scholar 

  • Wang JC, Dick JE . (2005). Cancer stem cells: lessons from leukemia. Trends Cell Biol 15: 494–501.

    CAS  Google Scholar 

  • Watkins DN, Berman DM, Burkholder SG, Wang B, Beachy PA, Baylin SB . (2003). Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. Nature 422: 313–317.

    CAS  Google Scholar 

  • Yanagi S, Kishimoto H, Kawahara K, Sasaki T, Sasaki M, Nishio M et al. (2007). Pten controls lung morphogenesis, bronchioalveolar stem cells, and onset of lung adenocarcinomas in mice. J Clin Invest 117: 2929–2940.

    CAS  Google Scholar 

  • Yang ZJ, Ellis T, Markant SL, Read TA, Kessler JD, Bourboulas M et al. (2008). Medulloblastoma can be initiated by deletion of patched in lineage-restricted progenitors or stem cells. Cancer Cell 14: 135–145.

    CAS  Google Scholar 

  • Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C et al. (2007). Let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell 131: 1109–1123.

    CAS  Google Scholar 

  • Zeng Z, Shi YX, Samudio IJ, Wang RY, Ling X, Frolova O et al. (2009). Targeting the leukemia microenvironment by CXCR4 inhibition overcomes resistance to kinase inhibitors and chemotherapy in AML. Blood 113: 6215–6224.

    CAS  Google Scholar 

  • Zeppernick F, Ahmadi R, Campos B, Dictus C, Helmke BM, Becker N et al. (2008). Stem cell marker CD133 affects clinical outcome in glioma patients. Clin Cancer Res 14: 123–129.

    CAS  Google Scholar 

  • Zhou BB, Zhang H, Damelin M, Geles KG, Grindley JC, Dirks PB . (2009). Tumour-initiating cells: challenges and opportunities for anticancer drug discovery. Nat Rev Drug Discov 8: 806–823.

    CAS  Google Scholar 

  • Zhu L, Gibson P, Currle DS, Tong Y, Richardson RJ, Bayazitov IT et al. (2009). Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation. Nature 457: 603–607.

    CAS  Google Scholar 

Download references

Acknowledgements

We thank Giuseppe Loreto for technical assistance with figures and tables. We thank the Italian Association for Cancer Research (AIRC) and the Marie Curie network project ‘ApopTrain’ (MRTN-CT-2006-035624) for supporting the lung cancer stem cell research.

Author information

Authors and Affiliations

  1. Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome, Italy

    A Eramo, T L Haas & R De Maria

  2. Mediterranean Institute of Oncology, Via Penninazzo 7, Viagrande, Catania, Italy

    T L Haas & R De Maria

Authors
  1. A Eramo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T L Haas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R De Maria
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R De Maria.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Eramo, A., Haas, T. & De Maria, R. Lung cancer stem cells: tools and targets to fight lung cancer. Oncogene 29, 4625–4635 (2010). https://doi.org/10.1038/onc.2010.207

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/onc.2010.207

Keywords

This article is cited by

Search

Advanced search

Quick links