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Cancer Stem Cells in Glioblastoma

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Stem Cells and Cancer Stem Cells, Volume 1

Part of the book series: Stem Cells and Cancer Stem Cells ((STEM,volume 1))

Abstract

Glioblastoma multiforme (GBM) is the most common adult malignant brain tumor and is comprised of a heterogeneous population of cells. Despite advanced surgical and medical therapies, the 2-year survival rate for patients with GBM remain only 10–25%. Recently, increasing evidence suggest that the progression of GBM is driven by a small subpopulation of tumor cells, termed cancer stem cells. These cancer stem cells have capability of self-renewal, proliferation, and differentiation into the phenotypically diverse populations of cells similar to those present in the original GBM. Furthermore, these cancer stem cells are able to form tumors and generate both neuron-like and glial-like progenies after implantation into the brains of SCID mice. Here, we summarize the methods of isolating cancer stem cells from GMB, and discuss the implications of the cancer stem cell hypothesis for understanding the origin and growth of GBM and development of new therapeutic strategies for the treatment of brain tumors.

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References

  • 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  PubMed  CAS  Google Scholar 

  • Bachoo RM, Maher EA, Ligon KL, Sharpless NE, Chan SS, You MJ, Tang Y, DeFrances J, Stover E, Weissleder R, Rowitch DH, Louis DN, DePinho RA (2002) Epidermal growth factor receptor and Ink4a/Arf: convergent mechanisms governing terminal differentiation and transformation along the neural stem cell to astrocyte axis. Cancer Cell 1:269–277

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Calabrese C, Poppleton H, Kocak M, Hogg TL, Fuller C, Hamner B, Oh EY, Gaber MW, Finklestein D, Allen M, Frank A, Bayazitov IT, Zakharenko SS, Gajjar A, Davidoff A, Gilbertson RJ (2007) A perivascular niche for brain tumor stem cells. Cancer Cell 11:69–82

    Article  PubMed  CAS  Google Scholar 

  • Dean M, Fojo T, Bates S (2005) Tumour stem cells and drug resistance. Nat Rev Cancer 5:275–284

    Article  PubMed  CAS  Google Scholar 

  • Dirks PB (2008) Brain tumor stem cells: bringing order to the chaos of brain cancer. J Clin Oncol 26:2916–2924

    Article  PubMed  Google Scholar 

  • Folkins C, Man S, Xu P, Shaked Y, Hicklin DJ, Kerbel RS (2007) Anticancer therapies combining antiangiogenic and tumor cell cytotoxic effects reduce the tumor stem-like cell fraction in glioma xenograft tumors. Cancer Res 67:3560–3564

    Article  PubMed  CAS  Google Scholar 

  • Fukaya R, Ohta S, Yamaguchi M, Fujii H, Kawakami Y, Kawase T, Toda M (2009) Isolation of cancer stem-like cells from a side population of a human glioblastoma cell line, SK-MG-1. Cancer Lett 291:150–157

    Article  PubMed  Google Scholar 

  • Galli R, Binda E, Orfanelli U, Cipelletti B, Gritti A, De Vitis S, Fiocco R, Foroni C, Dimeco F, Vescovi A (2004) Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res 64:7011–7021

    Article  PubMed  CAS  Google Scholar 

  • Hemmati HD, Nakano I, Lazareff JA, Masterman-Smith M, Geschwind DH, Bronner-Fraser M, Kornblum HI (2003) Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci USA 100:15178–15183

    Article  PubMed  CAS  Google Scholar 

  • Hoglinger GU, Rizk P, Muriel MP, Duyckaerts C, Oertel WH, Caille I, Hirsch EC (2004) Dopamine depletion impairs precursor cell proliferation in Parkinson disease. Nat Neurosci 7:726–735

    Article  PubMed  Google Scholar 

  • Holland EC, Celestino J, Dai C, Schaefer L, Sawaya RE, Fuller GN (2000) Combined activation of Ras and Akt in neural progenitors induces glioblastoma formation in mice. Nat Genet 25:55–57

    Article  PubMed  CAS  Google Scholar 

  • Ignatova TN, Kukekov VG, Laywell ED, Suslov ON, Vrionis FD, Steindler DA (2002) Human cortical glial tumors contain neural stem-like cells expressing astroglial and neuronal markers in vitro. Glia 39:193–206

    Article  PubMed  Google Scholar 

  • Kabos P, Ehtesham M, Kabosova A, Black KL, Yu JS (2002) Generation of neural progenitor cells from whole adult bone marrow. Exp Neurol 178:288–293

    Article  PubMed  CAS  Google Scholar 

  • Kondo T, Raff M (2000) Oligodendrocyte precursor cells reprogrammed to become multipotential CNS stem cells. Science 289:1754–1757

    Article  PubMed  CAS  Google Scholar 

  • Kondo T, Setoguchi T, Taga T (2004). Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc Natl Acad Sci USA 101:781–786

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Liu G, Yuan X, Zeng Z, Tunici P, Ng H, Abdulkadir IR, Lu L, Irvin D, Black KL, Yu JS (2006) Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma. Mol Cancer 5:67

    Article  PubMed  Google Scholar 

  • Liu Z, Martin LJ (2006) The adult neural stem and progenitor cell niche is altered in amyotrophic lateral sclerosis mouse brain. J Comp Neurol 497:468–488

    Article  PubMed  Google Scholar 

  • Nunes MC, Roy NS, Keyoung HM, Goodman RR, McKhann G 2nd, Jiang L, Kang J, Nedergaard M, Goldman SA (2003) Identification and isolation of multipotential neural progenitor cells from the subcortical white matter of the adult human brain. Nat Med 9:439–447

    Article  PubMed  CAS  Google Scholar 

  • Pardal R, Clarke MF, Morrison SJ (2003) Applying the principles of stem-cell biology to cancer. Nat Rev Cancer 3:895–902

    Article  PubMed  CAS  Google Scholar 

  • Qiang L, Yang Y, Ma YJ, Chen FH, Zhang LB, Liu W, Qi Q, Lu N, Tao L, Wang XT, You QD, Guo QL (2009) Isolation and characterization of cancer stem like cells in human glioblastoma cell lines. Cancer Lett 279:13–21

    Article  PubMed  CAS  Google Scholar 

  • Quinones-Hinojosa A, Sanai N, Gonzalez-Perez O, Garcia-Verdugo JM (2007) The human brain subventricular zone: stem cells in this niche and its organization. Neurosurg Clin N Am 18:15–20, vii

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Roy NS, Wang S, Jiang L, Kang J, Benraiss A, Harrison-Restelli C, Fraser RA, Couldwell WT, Kawaguchi A, Okano H, Nedergaard M, Goldman SA (2000) In vitro neurogenesis by progenitor cells isolated from the adult human hippocampus. Nat Med 6:271–277

    Article  PubMed  CAS  Google Scholar 

  • Sanai N, Tramontin AD, Quinones-Hinojosa A, Barbaro NM, Gupta N, Kunwar S, Lawton MT, McDermott MW, Parsa AT, Manuel-Garcia Verdugo J, Berger MS, Alvarez-Buylla A (2004) Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration. Nature 427:740–744

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432:396–401

    Article  PubMed  CAS  Google Scholar 

  • Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK,Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996

    Article  PubMed  CAS  Google Scholar 

  • Thored P, Arvidsson A, Cacci E, Ahlenius H, Kallur T, Darsalia V, Ekdahl CT, Kokaia Z, Lindvall O (2006) Persistent production of neurons from adult brain stem cells during recovery after stroke. Stem Cells 24:739–747

    Article  PubMed  CAS  Google Scholar 

  • Vescovi AL, Galli R, Reynolds BA (2006) Brain tumour stem cells. Nat Rev Cancer 6:425–436

    Article  PubMed  CAS  Google Scholar 

  • Weissman IL (2000) Stem cells: units of development, units of regeneration, and units in evolution. Cell 100:157–168

    Article  PubMed  CAS  Google Scholar 

  • Xu Q, Yuan X, Tunici P, Liu G, Fan X, Xu M, Hu J, Hwang JY, Farkas DL, Black KL, Yu JS (2009) Isolation of tumour stem-like cells from benign tumours. Br J Cancer 101:303–311

    Article  PubMed  CAS  Google Scholar 

  • Yuan X, Curtin J, Xiong Y, Liu G, Waschsmann-Hogiu S, Farkas DL, Black KL, Yu JS (2004) Isolation of cancer stem cells from adult glioblastoma multiforme. Oncogene 23:9392–9400

    Article  PubMed  CAS  Google Scholar 

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Correspondence to John S. Yu .

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© 2012 Springer Science+Business Media B.V.

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Hu, J., Yuan, X., Xu, Q., Wang, H., Black, K.L., Yu, J.S. (2012). Cancer Stem Cells in Glioblastoma. In: Hayat, M. (eds) Stem Cells and Cancer Stem Cells, Volume 1. Stem Cells and Cancer Stem Cells, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-1709-1_14

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