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Cancer Stem Cells: A Quick Walk Through the Concepts

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Cancer Stem Cells: Emerging Concepts and Future Perspectives in Translational Oncology

Abstract

Cancer stem cells (CSCs) are a subpopulation of tumor cells hypothesized to be largely responsible for the gene expression heterogeneity that exists within tumors. Since surviving CSCs have the capacity to regenerate tumor deposits, CSC chemoresistance represents an important clinical concern. CSCs have been shown to exploit a number of different mechanisms to exert resistance to chemotherapy. These mechanisms include increased DNA damage response, deregulation of apoptosis pathways, increased efflux transporter expression and increased expression of drug detoxification enzymes. Mounting experimental evidence suggests that successful cancer therapy must be directed against both CSCs and proliferating cells which make up the bulk of the tumor. In this regards, therapeutic approach based on combination of conventional therapies targeting bulk tumor cells and therapeutic strategies that selectively target CSCs would be of value in curing cancer.

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References

  • Abbott BL (2006) ABCG2 (BCRP): a cytoprotectant in normal and malignant stem cells. Clin Adv Hematol Oncol 4(1):63–72

    PubMed  Google Scholar 

  • Abdullah LN, Chow EK (2013) Mechanisms of chemoresistance in cancer stem cells. Clin Transl Med 2(1):3

    Article  PubMed Central  PubMed  Google Scholar 

  • Bao B, Ahmad A, Li Y, Azmi AS, Ali S, Banerjee S, Kong D, Sarkar FH (2012) Targeting CSCs within the tumor microenvironment for cancer therapy: a potential role of mesenchymal stem cells. Expert Opin Ther Targets 16(10):1041–1054

    Article  CAS  PubMed  Google Scholar 

  • Beachy PA, Karhadkar SS, Berman DM (2004) Tissue repair and stem cell renewal in carcinogenesis. Nature 432(7015):324–331

    Article  CAS  PubMed  Google Scholar 

  • Bertolini G, Roz L, Perego P, Tortoreto M, Fontanella E, Gatti L, Pratesi G, Fabbri A, Andriani F, Tinelli S, Roz E, Caserini R, Lo Vullo S, Camerini T, Mariani L, Delia D, Calabro E, Pastorino U, Sozzi G (2009) Highly tumorigenic lung cancer CD133+ cells display stem-like features and are spared by cisplatin treatment. Proc Natl Acad Sci USA 106(38):16281–16286

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bianchini C, Ciorba A, Pelucchi S, Piva R, Pastore A (2008) Head and neck cancer: the possible role of stem cells. Eur Arch Otorhinolaryngol 265(1):17–20

    Article  CAS  PubMed  Google Scholar 

  • Braakhuis BJ, Leemans CR, Brakenhoff RH (2005) Expanding fields of genetically altered cells in head and neck squamous carcinogenesis. Semin Cancer Biol 15(2):113–120

    Article  PubMed  Google Scholar 

  • Burger PE, Gupta R, Xiong X, Ontiveros CS, Salm SN, Moscatelli D, Wilson EL (2009) High aldehyde dehydrogenase activity: a novel functional marker of murine prostate stem/progenitor cells. Stem Cells 27(9):2220–2228

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Chen YC, Hsu HS, Chen YW, Tsai TH, How CK, Wang CY, Hung SC, Chang YL, Tsai ML, Lee YY, Ku HH, Chiou SH (2008) Oct-4 expression maintained cancer stem-like properties in lung cancer-derived CD133-positive cells. PLoS One 3(7), e2637

    Article  PubMed Central  PubMed  Google Scholar 

  • Chen WJ, Ho CC, Chang YL, Chen HY, Lin CA, Ling TY, Yu SL, Yuan SS, Chen YJ, Lin CY, Pan SH, Chou HY, Chang GC, Chu WC, Lee YM, Lee JY, Lee PJ, Li KC, Chen HW, Yang PC (2014) Cancer-associated fibroblasts regulate the plasticity of lung cancer stemness via paracrine signalling. Nat Commun 5:3472

    PubMed  Google Scholar 

  • Chiou SH, Wang ML, Chou YT, Chen CJ, Hong CF, Hsieh WJ, Chang HT, Chen YS, Lin TW, Hsu HS, Wu CW (2010) Coexpression of Oct4 and Nanog enhances malignancy in lung adenocarcinoma by inducing cancer stem cell-like properties and epithelial-mesenchymal transdifferentiation. Cancer Res 70(24):10433–10444

    Article  CAS  PubMed  Google Scholar 

  • Collins R, Fenwick E, Trowman R, Perard R, Norman G, Light K, Birtle A, Palmer S, Riemsma R (2007) A systematic review and economic model of the clinical effectiveness and cost-effectiveness of docetaxel in combination with prednisone or prednisolone for the treatment of hormone-refractory metastatic prostate cancer. Health Technol Assess 11(2):1–179, iii-iv, xv-xviii

    Article  Google Scholar 

  • Datta RS, Gutteridge A, Swanton C, Maley CC, Graham TA (2013) Modelling the evolution of genetic instability during tumour progression. Evol Appl 6(1):20–33

    Article  CAS  Google Scholar 

  • Forastiere A, Koch W, Trotti A, Sidransky D (2001) Head and neck cancer. N Engl J Med 345(26):1890–1900

    Article  CAS  PubMed  Google Scholar 

  • Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer CG, Liu S, Schott A, Hayes D, Birnbaum D, Wicha MS, Dontu G (2007) ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1(5):555–567

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • He B, Barg RN, You L, Xu Z, Reguart N, Mikami I, Batra S, Rosell R, Jablons DM (2005) Wnt signaling in stem cells and non-small-cell lung cancer. Clin Lung Cancer 7(1):54–60

    Article  CAS  PubMed  Google Scholar 

  • Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M, Bruns CJ, Heeschen C (2007) Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 1(3):313–323

    Article  CAS  PubMed  Google Scholar 

  • Hollier BG, Evans K, Mani SA (2009) The epithelial-to-mesenchymal transition and cancer stem cells: a coalition against cancer therapies. J Mammary Gland Biol Neoplasia 14(1):29–43

    Article  PubMed  Google Scholar 

  • Huang EH, Hynes MJ, Zhang T, Ginestier C, Dontu G, Appelman H, Fields JZ, Wicha MS, Boman BM (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(8):3382–3389

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Insan MB, Jaitak V (2014) New approaches to target cancer stem cells: current scenario. Mini Rev Med Chem 14(1):20–34

    Article  CAS  PubMed  Google Scholar 

  • Jordan NV, Johnson GL, Abell AN (2011) Tracking the intermediate stages of epithelial-mesenchymal transition in epithelial stem cells and cancer. Cell Cycle 10(17):2865–2873

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kim MA, Lee HS, Lee HE, Kim JH, Yang HK, Kim WH (2009) Prognostic importance of epithelial-mesenchymal transition-related protein expression in gastric carcinoma. Histopathology 54(4):442–451

    Article  PubMed  Google Scholar 

  • Klonisch T, Wiechec E, Hombach-Klonisch S, Ande SR, Wesselborg S, Schulze-Osthoff K, Los M (2008) Cancer stem cell markers in common cancers – therapeutic implications. Trends Mol Med 14(10):450–460

    Article  CAS  PubMed  Google Scholar 

  • Krantz SB, Shields MA, Dangi-Garimella S, Munshi HG, Bentrem DJ (2012) Contribution of epithelial-to-mesenchymal transition and cancer stem cells to pancreatic cancer progression. J Surg Res 173(1):105–112

    Article  PubMed Central  PubMed  Google Scholar 

  • Levin TG, Powell AE, Davies PS, Silk AD, Dismuke AD, Anderson EC, Swain JR, Wong MH (2010) Characterization of the intestinal cancer stem cell marker CD166 in the human and mouse gastrointestinal tract. Gastroenterology 139(6):2072–2082, e2075

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF, Simeone DM (2007) Identification of pancreatic cancer stem cells. Cancer Res 67(3):1030–1037

    Article  CAS  PubMed  Google Scholar 

  • Lobo NA, Shimono Y, Qian D, Clarke MF (2007) The biology of cancer stem cells. Annu Rev Cell Dev Biol 23:675–699

    Article  CAS  PubMed  Google Scholar 

  • Longley DB, Johnston PG (2005) Molecular mechanisms of drug resistance. J Pathol 205(2):275–292

    Article  CAS  PubMed  Google Scholar 

  • Lugli A, Iezzi G, Hostettler I, Muraro MG, Mele V, Tornillo L, Carafa V, Spagnoli G, Terracciano L, Zlobec I (2010) Prognostic impact of the expression of putative cancer stem cell markers CD133, CD166, CD44s, EpCAM, and ALDH1 in colorectal cancer. Br J Cancer 103(3):382–390

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133(4):704–715

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mareel M, Boterberg T, Noe V, Van Hoorde L, Vermeulen S, Bruyneel E, Bracke M (1997) E-cadherin/catenin/cytoskeleton complex: a regulator of cancer invasion. J Cell Physiol 173(2):271–274

    Article  CAS  PubMed  Google Scholar 

  • Marotta LL, Polyak K (2009) Cancer stem cells: a model in the making. Curr Opin Genet Dev 19(1):44–50

    Article  PubMed  Google Scholar 

  • Massague J (2008) TGFbeta in cancer. Cell 134(2):215–230

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Maugeri-Sacca M, Vigneri P, De Maria R (2011) Cancer stem cells and chemosensitivity. Clin Cancer Res 17(15):4942–4947

    Article  CAS  PubMed  Google Scholar 

  • Miki J, Furusato B, Li H, Gu Y, Takahashi H, Egawa S, Sesterhenn IA, McLeod DG, Srivastava S, Rhim JS (2007) Identification of putative stem cell markers, CD133 and CXCR4, in hTERT-immortalized primary nonmalignant and malignant tumor-derived human prostate epithelial cell lines and in prostate cancer specimens. Cancer Res 67(7):3153–3161

    Article  CAS  PubMed  Google Scholar 

  • Miraglia S, Godfrey W, Yin AH, Atkins K, Warnke R, Holden JT, Bray RA, Waller EK, Buck DW (1997) A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning. Blood 90(12):5013–5021

    CAS  PubMed  Google Scholar 

  • Prince ME, Sivanandan R, Kaczorowski A, Wolf GT, Kaplan MJ, Dalerba P, Weissman IL, Clarke MF, Ailles LE (2007) Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci USA 104(3):973–978

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Shipitsin M, Polyak K (2008) The cancer stem cell hypothesis: in search of definitions, markers, and relevance. Lab Invest 88(5):459–463

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Shipitsin M, Campbell LL, Argani P, Weremowicz S, Bloushtain-Qimron N, Yao J, Nikolskaya T, Serebryiskaya T, Beroukhim R, Hu M, Halushka MK, Sukumar S, Parker LM, Anderson KS, Harris LN, Garber JE, Richardson AL, Schnitt SJ, Nikolsky Y, Gelman RS, Polyak K (2007) Molecular definition of breast tumor heterogeneity. Cancer Cell 11(3):259–273

    Article  CAS  PubMed  Google Scholar 

  • Tan BT, Park CY, Ailles LE, Weissman IL (2006) The cancer stem cell hypothesis: a work in progress. Lab Invest 86(12):1203–1207

    Article  CAS  PubMed  Google Scholar 

  • Thiery JP (2002) Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2(6):442–454

    Article  CAS  PubMed  Google Scholar 

  • Togawa H, Nakanishi K, Mukaiyama H, Hama T, Shima Y, Sako M, Miyajima M, Nozu K, Nishii K, Nagao S, Takahashi H, Iijima K, Yoshikawa N (2011) Epithelial-to-mesenchymal transition in cyst lining epithelial cells in an orthologous PCK rat model of autosomal-recessive polycystic kidney disease. Am J Physiol Renal Physiol 300(2):F511–F520

    Article  CAS  PubMed  Google Scholar 

  • Varjosalo M, Taipale J (2008) Hedgehog: functions and mechanisms. Genes Dev 22(18):2454–2472

    Article  CAS  PubMed  Google Scholar 

  • Visvader JE, Lindeman GJ (2008) Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer 8(10):755–768

    Article  CAS  PubMed  Google Scholar 

  • Weichert W, Knosel T, Bellach J, Dietel M, Kristiansen G (2004) ALCAM/CD166 is overexpressed in colorectal carcinoma and correlates with shortened patient survival. J Clin Pathol 57(11):1160–1164

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wu KJ (2011) Direct activation of Bmi1 by Twist1: implications in cancer stemness, epithelial-mesenchymal transition, and clinical significance. Chang Gung Med J 34(3):229–238

    PubMed  Google Scholar 

  • Wu Y, Wu PY (2009) CD133 as a marker for cancer stem cells: progresses and concerns. Stem Cells Dev 18(8):1127–1134

    Article  CAS  PubMed  Google Scholar 

  • Yang J, Weinberg RA (2008) Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell 14(6):818–829

    Article  CAS  PubMed  Google Scholar 

  • Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, Savagner P, Gitelman I, Richardson A, Weinberg RA (2004) Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117(7):927–939

    Article  CAS  PubMed  Google Scholar 

  • Zhou D, Shao L, Spitz DR (2014) Reactive oxygen species in normal and tumor stem cells. Adv Cancer Res 122:1–67

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, 1411713116, Iran

    Katayoon Pakravan, Mohammad Amin Mahjoub, Babak Jahangiri & Sadegh Babashah

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  1. Katayoon Pakravan
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  2. Mohammad Amin Mahjoub
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  3. Babak Jahangiri
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  4. Sadegh Babashah
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Correspondence to Sadegh Babashah .

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Editors and Affiliations

  1. Faculty of Biol. Scs. Dept. of Mol. Gen., Tarbiat Modares University , Tehran, Iran

    Sadegh Babashah

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Pakravan, K., Mahjoub, M.A., Jahangiri, B., Babashah, S. (2015). Cancer Stem Cells: A Quick Walk Through the Concepts. In: Babashah, S. (eds) Cancer Stem Cells: Emerging Concepts and Future Perspectives in Translational Oncology. Springer, Cham. https://doi.org/10.1007/978-3-319-21030-8_1

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