Skip to main content
SpringerLink
Log in

Glioma Cell Lines: Role of Cancer Stem Cells

  • Chapter
  • First Online:
Tumors of the Central Nervous System, Volume 1

Part of the book series: Tumors of the Central Nervous System ((TCNS,volume 1))

  • 1881 Accesses

Abstract

In this chapter, we review the cancer stem cell hypothesis and discuss implications for this paradigm in considering whether glioma cell lines contain bonafide cancer stem cells, the source material used for tissue culture, and experimental methods used in preclinical research. We identify three key modifications to standard tissue culture protocols that allow for enrichment of cancer stem cells that closely reflect the genetics, gene expression, and phenotype of the primary tumors. These modifications are the use of: (i) primary tumors exclusively cultured in serum-free media, (ii) cellular adherence to artificial extracellular matrix, (iii) physiologic oxygen in tissue culture. Widespread acceptance of this tissue culture protocol should lead to in vitro and in vivo preclinical models that more faithfully recapitulate the human disease and thereby increase the rate of successful therapeutic development.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • 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 

  • Bez A, Corsini E, Curti D, Biggiogera M, Colombo A, Nicosia RF, Pagano SF, Parati EA (2003) Neurosphere and neurosphere-forming cells: morphological and ultrastructural characterization. Brain Res 993:18–29

    Article  PubMed  CAS  Google Scholar 

  • Bleau A-M, Hambardzumyan D, Ozawa T, Fomchenko EI, Huse JT, Brennan CW, Holland EC (2009) PTEN/PI3K/akt pathway regulates the side population phenotype and ABCG2 activity in glioma tumor stem-like cells. Cell Stem Cell 4:226–235

    Article  PubMed  CAS  Google Scholar 

  • Clarke MF, Dick JE, Dirks PB, Eaves C, Jamieson C, Jones D, Visvader J, Weissman IL, Wahl G (2006) Cancer stem cells–perspectives on current status and future directions: AACR workshop on cancer stem cells. Cancer Res 66:9339–9344

    Article  PubMed  CAS  Google Scholar 

  • Clement V, Marino D, Cudalbu C, Hamou M-F, Mlynarik V, de Tribolet N, Dietrich P-Y, Gruetter R, Hegi ME, Radovanovic I (2010) Marker-independent identification of glioma-initiating cells. Nat Methods 7:224–228

    Article  PubMed  CAS  Google Scholar 

  • Erecinska M, Silver IA (2001) Tissue oxygen tension and brain sensitivity to hypoxia. Respir Physiol 128:263–276

    Article  PubMed  CAS  Google Scholar 

  • Evans SM, Judy KD, Dunphy I, Jenkins WT, Hwang WT, Nelson PT, Lustig RA, Jenkins K, Magarelli DP, Hahn SM, Collins RA, Grady MS, Koch CJ (2004) Hypoxia is important in the biology and aggression of human glial brain tumors. Clin Cancer Res 10:8177–8184

    Article  PubMed  CAS  Google Scholar 

  • Fael Al-Mayhani TM, Ball SLR, Zhao J-W, Fawcett J, Ichimura K, Collins PV, Watts C (2009) An efficient method for derivation and propagation of glioblastoma cell lines that conserves the molecular profile of their original tumours. J Neurosci Methods 176:192–199

    Article  PubMed  CAS  Google Scholar 

  • Fine RL, Chen J, Balmaceda C, Bruce JN, Huang M, Desai M, Sisti MB, McKhann GM, Goodman RR, Bertino JS Jr., Nafziger AN, Fetell MR (2006) Randomized study of paclitaxel and tamoxifen deposition into human brain tumors: implications for the treatment of metastatic brain tumors. Clin Cancer Res 12:5770–5776

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Gilbertson RJ, Rich JN (2007) Making a tumour’s bed: glioblastoma stem cells and the vascular niche. Nat Rev Cancer 7:733–736

    Article  PubMed  CAS  Google Scholar 

  • Griguer CE, Oliva CR, Gobin E, Marcorelles P, Benos DJ, Lancaster JR Jr, Gillespie GY (2008) CD133 is a marker of bioenergetic stress in human glioma. PLoS One 3:e3655

    Article  PubMed  Google Scholar 

  • Günther HS, Schmidt NO, Phillips HS, Kemming D, Kharbanda S, Soriano R, Modrusan Z, Meissner H, Westphal M, Lamszus K (2008) Glioblastoma-derived stem cell-enriched cultures form distinct subgroups according to molecular and phenotypic criteria. Oncogene 27:2897–2909

    Article  PubMed  Google Scholar 

  • Hope KJ, Jin L, Dick JE (2004) Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nat Immunol 5:738–743

    Article  PubMed  CAS  Google Scholar 

  • Jain RK, di Tomaso E, Duda DG, Loeffler JS, Sorensen AG, Batchelor TT (2007) Angiogenesis in brain tumours. Nat Rev Neurosci 8:610–622

    Article  PubMed  CAS  Google Scholar 

  • Kelly JJP, Stechishin O, Chojnacki A, Lun X, Sun B, Senger DL, Forsyth P, Auer RN, Dunn JF, Cairncross JG, Parney IF, Weiss S (2009) Proliferation of human glioblastoma stem cells occurs independently of exogenous mitogens. Stem Cells 27:1722–1733

    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 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 

  • Lee J, Kotliarova S, Kotliarov Y, Li A, Su Q, Donin NM, Pastorino S, Purow BW, Christopher N, Zhang W, Park JK, Fine HA (2006) Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines. Cancer Cell 9:391–403

    Article  PubMed  CAS  Google Scholar 

  • Li Z, Bao S, Wu Q, Wang H, Eyler C, Sathornsumetee S, Shi Q, Cao Y, Lathia J, McLendon RE, Hjelmeland AB, Rich JN (2009) Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells. Cancer Cell 15:501–513

    Google Scholar 

  • Mao X-G, Zhang X, Xue X-Y, Guo G, Wang P, Zhang W, Fei Z, Zhen H-N, You S-W, Yang H (2009) Brain tumor stem-like cells identified by neural stem cell marker CD15. Transl Oncol 2:247–257

    PubMed  Google Scholar 

  • McCord AM, Jamal M, Shankavarum UT, Lang FF, Camphausen K, Tofilon PJ (2009) Physiologic oxygen concentration enhances the stem-like properties of CD133+ human glioblastoma cells in vitro. Mol Cancer Res 7:489–497

    Article  PubMed  CAS  Google Scholar 

  • Olin MR, Andersen BM, Zellmer DM, Grogan PT, Popescu FE, Xiong Z, Forster CL, Seiler C, SantaCruz KS, Chen W, Blazar BR, Ohlfest JR (2010) Superior efficacy of tumor cell vaccines grown in physiologic oxygen. Clin Cancer Res 16:4800–4808

    Google Scholar 

  • Patrawala L, Calhoun T, Schneider-Broussard R, Zhou J, Claypool K, Tang DG (2005) Side population is enriched in tumorigenic, stem-like cancer cells, whereas ABCG2+ and ABCG2- cancer cells are similarly tumorigenic. Cancer Res 65:6207–6219

    Article  PubMed  CAS  Google Scholar 

  • Phillips HS, Kharbanda S, Chen R, Forrest WF, Soriano RH, Wu TD, Misra A, Nigro JM, Colman H, Soroceanu L, Williams PM, Modrusan Z, Feuerstein BG, Aldape KD (2006) Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell 9:157–173

    Article  PubMed  CAS  Google Scholar 

  • Platet N, Liu SY, Atifi ME, Oliver L, Vallette FM, Berger F, Wion D (2007) Influence of oxygen tension on CD133 phenotype in human glioma cell cultures. Cancer Lett 258:286–290

    Article  PubMed  CAS  Google Scholar 

  • Pollard SM, Yoshikawa K, Clarke ID, Danovi D, Stricker S, Russell R, Bayani J, Head R, Lee M, Bernstein M, Squire JA, Smith A, Dirks P (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

    Article  PubMed  CAS  Google Scholar 

  • Quintana E, Shackleton M, Sabel MS, Fullen DR, Johnson TM, Morrison SJ (2008) Efficient tumour formation by single human melanoma cells. Nature 456:593–598

    Article  PubMed  CAS  Google Scholar 

  • Reynolds BA, Rietze RL (2005) Neural stem cells and neurospheres–re-evaluating the relationship. Nat Methods 2:333–336

    Article  PubMed  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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Son MJ, Woolard K, Nam D-H, Lee J, Fine HA (2009) SSEA-1 is an enrichment marker for tumor-initiating cells in human glioblastoma. Cell Stem Cell 4:440–452

    Article  PubMed  CAS  Google Scholar 

  • Suslov ON, Kukekov VG, Ignatova TN, Steindler DA (2002) Neural stem cell heterogeneity demonstrated by molecular phenotyping of clonal neurospheres. Proc Natl Acad Sci USA 99:14506–14511

    Article  PubMed  CAS  Google Scholar 

  • Wu A, Oh S, Wiesner SM, Ericson K, Chen L, Hall WA, Champoux PE, Low WC, Ohlfest JR (2008) Persistence of CD133+ cells in human and mouse glioma cell lines: detailed characterization of GL261 glioma cells with cancer stem cell-like properties. Stem Cells Dev 17:173–184

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurosurgery, University of Minnesota Medical School, Minneapolis, MN, 55455, USA

    John R. Ohlfest & Stacy A. Decker

Authors
  1. John R. Ohlfest
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stacy A. Decker
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John R. Ohlfest .

Editor information

Editors and Affiliations

  1. Dept. Biological Sciences, Kean University, 1000 Moris Avenue, Union, 07083, New Jersey, USA

    M. A. Hayat

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Ohlfest, J.R., Decker, S.A. (2011). Glioma Cell Lines: Role of Cancer Stem Cells. In: Hayat, M. (eds) Tumors of the Central Nervous System, Volume 1. Tumors of the Central Nervous System, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0344-5_21

Download citation

  • DOI: https://doi.org/10.1007/978-94-007-0344-5_21

  • Published:

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-007-0343-8

  • Online ISBN: 978-94-007-0344-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation