Abstract
Two theories describe the development of cancer. The clonal evolution theory posits that cancer arises from a single cell of origin, and hat progression of the cancer occurs due to the acquisition of genetic abnormalities within the original clone, allowing the sequential selection of more and more aggressive sublines; whereas the cancer stem cell theory posits that cancer cells are heterogeneous, and that only the cancer stem cell subset of tumor cells is able to extensively proliferate and metastasize. Stem cells occur normally in human beings. Adult somatic stem cells, lacking sufficient telomerase activity to prevent telomere loss, do not have the capacity to replicate indefinitely. Pluripotent adult somatic stem cells, with their limited ability to self-renew, have been found in many mature tissues, including lung. These cells are thought to be responsible for tissue regeneration and repair. Adult stem cells are believed to localize in their respective tissues in a special microenvironment—the so-called stem cell niche. These adult somatic stem cells are considered to have an increased risk for malignant transformation. The concept of cancer arising from hypothetical rare cells, with the stem cell properties of self-renewal and differentiation into progenitors, that exclusively maintain neoplastic clones—so called cancer stem cells—has already been acknowledged for hematologic malignancies. Many solid tumors are also thought to arise from cancer stem cells; specifically, originating from organ-specific stem cells. The concept of cancer stem cells is based on the principle that, in the multistep process of undergoing malignant transformation, a cell must be able to self-renew in order to accumulate enough mutations to transform into a malignant cell. These cancer stem cells allow for the propagation of cancer cells that retain the primary tumor’s diverse marker profile.
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References
Rivera C, Rivera S, Loriot Y, Vozenin MC, Deutsch E. Lung cancer stem cell: new insights on experimental models and preclinical data. J Oncol. 2011;2011: 549181.
Campbell LL, Polyak K. Breast tumor heterogeneity: cancer stem cells or clonal evolution? Cell Cycle. 2007;6:2332–8.
Nowell PC. The clonal evolution of tumor cell populations. Science. 1976;194:23–8.
Wicha MS, Liu S, Dontu G. Cancer stem cells: an old idea—a paradigm shift. Cancer Res. 2006;66:1883–90; discussion 1895–6.
Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414: 105–11.
Reyes M, Lund T, Lenvik T, Aguiar D, Koodie L, Verfaillie CM. Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells. Blood. 2001;98:2615–25.
Soltysova A, Altanerova V, Altaner C. Cancer stem cells. Neoplasma. 2005;52:435–40.
Pathak S, Multani AS. Aneuploidy, stem cells and cancer. EXS. 2006;96:49–64.
Guo W, Lasky III JL, Wu H. Cancer stem cells. Pediatr Res. 2006;59:59R–64.
Schwarz-Cruz-y-Celis A, Melendez-Zajgla J. Cancer stem cells. Rev Invest Clin. 2011;63:179–86.
Snyder EY, Hinman LM, Kalichman MW. Can science resolve the ethical impasse in stem cell research? Nat Biotechnol. 2006;24:397–400.
Brown M. No ethical bypass of moral status in stem cell research. Bioethics 2011, Jul 4 [EPub ahead of print].
Sherley JL. Asymmetric cell kinetics genes: the key to expansion of adult stem cells in culture. ScientificWorldJournal. 2002;2:1906–21.
Sotiropoulou PA, Candi A, Blanpain C. The majority of multipotent epidermal stem cells do not protect their genome by asymmetrical chromosome segregation. Stem Cells. 2008;26:2964–73.
Mattis VB, Svendsen CN. Induced pluripotent stem cells: a new revolution for clinical neurology? Lancet Neurol. 2011;10:383–94.
Romano G. Stem cell transplantation therapy: controversy over ethical issues and clinical relevance. Drug News Perspect. 2004;17:637–45.
Singbrant S, Askmyr M, Purton LE, Walkley CR. Defining the hematopoietic stem cell niche: the chicken and the egg conundrum. J Cell Biochem. 2011;112:1486–90.
Kiefer JC. Primer and interviews: the dynamic stem cell niche. Dev Dyn. 2011;240:737–43.
Okamoto OK. Cancer stem cell genomics: the quest for early markers of malignant progression. Expert Rev Mol Diagn. 2009;9:545–54.
Mohseny AB, Hogendoorn PC. Concise review: mesenchymal tumors: when stem cells go mad. Stem Cells. 2011;29:397–403.
Wang JC, Dick JE. Cancer stem cells: lessons from leukemia. Trends Cell Biol. 2005;15:494–501.
Cooper LJ, Shannon KM, Loken MR, Weaver M, Stephens K, Sievers EL. Evidence that juvenile myelomonocytic leukemia can arise from a pluripotential stem cell. Blood. 2000;96:2310–3.
Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997;3:730–7.
Guan Y, Gerhard B, Hogge DE. Detection, isolation, and stimulation of quiescent primitive leukemic progenitor cells from patients with acute myeloid leukemia (AML). Blood. 2003;101:3142–9.
Simonsson B, Hjorth-Hansen H, Bjerrum OW, Porkka K. Interferon alpha for treatment of chronic myeloid leukemia. Curr Drug Targets. 2011;12:420–8.
Berns A. Stem cells for lung cancer? Cell. 2005;121:811–3.
Fabrizi E, di Martino S, Pelacchi F, Ricci-Vitiani L. Therapeutic implications of colon cancer stem cells. World J Gastroenterol. 2010;16:3871–7.
Welte Y, Adjaye J, Lehrach HR, Regenbrecht CR. Cancer stem cells in solid tumors: elusive or illusive? Cell Commun Signal. 2010;8:6.
D’Angelo RC, Wicha MS. Stem cells in normal development and cancer. Prog Mol Biol Transl Sci. 2010;95:113–58.
Nguyen PK, Nag D, Wu JC. Methods to assess stem cell lineage, fate and function. Adv Drug Deliv Rev. 2010;62:1175–86.
Houghton J, Stoicov C, Nomura S, et al. Gastric cancer originating from bone marrow-derived cells. Science. 2004;306:1568–71.
Singh SK, Hawkins C, Clarke ID, et al. Identification of human brain tumour initiating cells. Nature. 2004;432:396–401.
Federici G, Espina V, Liotta L, Edmiston KH. Breast cancer stem cells: a new target for therapy. Oncology (Williston Park). 2011;25:25–8, 30.
Soltanian S, Matin MM. Cancer stem cells and cancer therapy. Tumour Biol. 2011;32:425–40.
Pardal R, Clarke MF, Morrison SJ. Applying the principles of stem-cell biology to cancer. Nat Rev Cancer. 2003;3:895–902.
Perona R, Lopez-Ayllon BD, de Castro Carpeno J, Belda-Iniesta C. A role for cancer stem cells in drug resistance and metastasis in non-small-cell lung cancer. Clin Transl Oncol. 2011;13:289–93.
Zhao Z, Zuber J, Diaz-Flores E, et al. p53 loss promotes acute myeloid leukemia by enabling aberrant self-renewal. Genes Dev. 2010;24:1389–402.
Nakagawara A, Ohira M. Comprehensive genomics linking between neural development and cancer: neuroblastoma as a model. Cancer Lett. 2004;204:213–24.
Trumpp A, Wiestler OD. Mechanisms of disease: cancer stem cells—targeting the evil twin. Nat Clin Pract Oncol. 2008;5:337–47.
Florian IS, Tomuleasa C, Soritau O, et al. Cancer stem cells and malignant gliomas. From pathophysiology to targeted molecular therapy. J BUON. 2011;16:16–23.
Li X, Lewis MT, Huang J, et al. Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J Natl Cancer Inst. 2008;100:672–9.
Tu SM, Lin SH, Logothetis CJ. Stem-cell origin of metastasis and heterogeneity in solid tumours. Lancet Oncol. 2002;3:508–13.
van Klaveren RJ, van’t Westeinde SC, de Hoop BJ, Hoogsteden HC. Stem cells and the natural history of lung cancer: implications for lung cancer screening. Clin Cancer Res. 2009;15:2215–8.
Chen Y, Peng C, Sullivan C, Li D, Li S. Critical molecular pathways in cancer stem cells of chronic myeloid leukemia. Leukemia. 2010;24:1545–54.
Miller SJ, Lavker RM, Sun TT. Interpreting epithelial cancer biology in the context of stem cells: tumor properties and therapeutic implications. Biochim Biophys Acta. 2005;1756:25–52.
Woodward WA, Chen MS, Behbod F, Rosen JM. On mammary stem cells. J Cell Sci. 2005;118:3585–94.
Reya T, Clevers H. Wnt signalling in stem cells and cancer. Nature. 2005;434:843–50.
Tai MH, Chang CC, Kiupel M, Webster JD, Olson LK, Trosko JE. Oct4 expression in adult human stem cells: evidence in support of the stem cell theory of carcinogenesis. Carcinogenesis. 2005;26:495–502.
Bhardwaj G, Murdoch B, Wu D, et al. Sonic hedgehog induces the proliferation of primitive human hematopoietic cells via BMP regulation. Nat Immunol. 2001;2:172–80.
Willert K, Brown JD, Danenberg E, et al. Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature. 2003;423:448–52.
Taipale J, Beachy PA. The Hedgehog and Wnt signalling pathways in cancer. Nature. 2001;411:349–54.
Lahad JP, Mills GB, Coombes KR. Stem cell-ness: a “magic marker” for cancer. J Clin Invest. 2005;115: 1463–7.
Jamora C, DasGupta R, Kocieniewski P, Fuchs E. Links between signal transduction, transcription and adhesion in epithelial bud development. Nature. 2003;422:317–22.
Beachy PA, Karhadkar SS, Berman DM. Tissue repair and stem cell renewal in carcinogenesis. Nature. 2004;432:324–31.
Nichols J, Zevnik B, Anastassiadis K, et al. Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell. 1998;95:379–91.
Donovan PJ. High Oct-ane fuel powers the stem cell. Nat Genet. 2001;29:246–7.
Hochedlinger K, Yamada Y, Beard C, Jaenisch R. Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues. Cell. 2005;121:465–77.
Park IK, Qian D, Kiel M, et al. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature. 2003;423:302–5.
Valk-Lingbeek ME, Bruggeman SW, van Lohuizen M. Stem cells and cancer; the polycomb connection. Cell. 2004;118:409–18.
Glinsky GV, Berezovska O, Glinskii AB. Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer. J Clin Invest. 2005;115:1503–21.
Perkins AS, Mercer JA, Jenkins NA, Copeland NG. Patterns of Evi-1 expression in embryonic and adult tissues suggest that Evi-1 plays an important regulatory role in mouse development. Development. 1991;111:479–87.
Yuasa H, Oike Y, Iwama A, et al. Oncogenic transcription factor Evi1 regulates hematopoietic stem cell proliferation through GATA-2 expression. EMBO J. 2005;24:1976–87.
Park IK, He Y, Lin F, et al. Differential gene expression profiling of adult murine hematopoietic stem cells. Blood. 2002;99:488–98.
Shimizu S, Nagasawa T, Katoh O, Komatsu N, Yokota J, Morishita K. EVI1 is expressed in megakaryocyte cell lineage and enforced expression of EVI1 in UT-7/GM cells induces megakaryocyte differentiation. Biochem Biophys Res Commun. 2002;292:609–16.
Galmozzi E, Facchetti F, La Porta CA. Cancer stem cells and therapeutic perspectives. Curr Med Chem. 2006;13:603–7.
Jamieson CH, Ailles LE, Dylla SJ, et al. Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. N Engl J Med. 2004;351: 657–67.
Molofsky AV, He S, Bydon M, Morrison SJ, Pardal R. Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and p19Arf senescence pathways. Genes Dev. 2005;19:1432–7.
Reya T, Duncan AW, Ailles L, et al. A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature. 2003;423:409–14.
Brabletz T, Jung A, Reu S, et al. Variable beta-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment. Proc Natl Acad Sci U S A. 2001;98:10356–61.
Brabletz T, Jung A, Spaderna S, Hlubek F, Kirchner T. Opinion: migrating cancer stem cells—an integrated concept of malignant tumour progression. Nat Rev Cancer. 2005;5:744–9.
Kondo T, Setoguchi T, Taga T. Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc Natl Acad Sci U S A. 2004;101:781–6.
Dick JE. Breast cancer stem cells revealed. Proc Natl Acad Sci U S A. 2003;100:3547–9.
Kim CF, Jackson EL, Woolfenden AE, et al. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell. 2005;121:823–35.
Hemmati HD, Nakano I, Lazareff JA, et al. Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci U S A. 2003;100:15178–83.
Singh SK, Clarke ID, Terasaki M, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res. 2003;63:5821–8.
Pitt BR, Ortiz LA. Stem cells in lung biology. Am J Physiol Lung Cell Mol Physiol. 2004;286:L621–3.
Haura EB. Is repetitive wounding and bone marrow-derived stem cell mediated-repair an etiology of lung cancer development and dissemination? Med Hypotheses. 2006;67:951–6.
Cockburn MG, Wu AH, Bernstein L. Etiologic clues from the similarity of histology-specific trends in esophageal and lung cancers. Cancer Causes Control. 2005;16:1065–74.
Brooks DR, Austin JH, Heelan RT, et al. Influence of type of cigarette on peripheral versus central lung cancer. Cancer Epidemiol Biomarkers Prev. 2005;14:576–81.
Popper HH. Bronchiolitis, an update. Virchows Arch. 2000;437:471–81.
Ullmann R, Bongiovanni M, Halbwedl I, et al. Bronchiolar columnar cell dysplasia—genetic analysis of a novel preneoplastic lesion of peripheral lung. Virchows Arch. 2003;442:429–36.
Borczuk AC, Gorenstein L, Walter KL, Assaad AA, Wang L, Powell CA. Non-small-cell lung cancer molecular signatures recapitulate lung developmental pathways. Am J Pathol. 2003;163:1949–60.
Eramo A, Haas TL, De Maria R. Lung cancer stem cells: tools and targets to fight lung cancer. Oncogene. 2010;29:4625–35.
Jiang F, Qiu Q, Khanna A, et al. Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer. Mol Cancer Res. 2009;7:330–8.
Sholl LM, Long KB, Hornick JL. Sox2 expression in pulmonary non-small cell and neuroendocrine carcinomas. Appl Immunohistochem Mol Morphol. 2010;18:55–61.
Pantel K, Alix-Panabieres C, Riethdorf S. Cancer micrometastases. Nat Rev Clin Oncol. 2009;6:339–51.
Aktas B, Tewes M, Fehm T, Hauch S, Kimmig R, Kasimir-Bauer S. Stem cell and epithelial-mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients. Breast Cancer Res. 2009;11:R46.
Song W, Li H, Tao K, et al. Expression and clinical significance of the stem cell marker CD133 in hepatocellular carcinoma. Int J Clin Pract. 2008;62:1212–8.
Pallini R, Ricci-Vitiani L, Banna GL, et al. Cancer stem cell analysis and clinical outcome in patients with glioblastoma multiforme. Clin Cancer Res. 2008;14:8205–12.
Bao S, Wu Q, McLendon RE, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006;444:756–60.
Ishikawa F, Yoshida S, Saito Y, et al. Chemotherapy-resistant human AML stem cells home to and engraft within the bone-marrow endosteal region. Nat Biotechnol. 2007;25:1315–21.
Kajstura J, Rota M, Hall SR, et al. Evidence for human lung stem cells. N Engl J Med. 2011;364:1795–806.
Lung stem cells: looking beyond the hype. Nat Med. 2011;17:788–9.
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Allen, T.C. (2012). Lung Cancer Stem Cells. In: Cagle, P., et al. Molecular Pathology of Lung Cancer. Molecular Pathology Library, vol 6. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3197-8_4
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