Skip to main content
SpringerLink
Log in

Markers of Stem Cells in Gliomas

  • 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))

  • 1860 Accesses

Abstract

Gliomas are the most common neoplasms of the Central Nervous System (CNS) and a frequent cause of mental impairment and death. Despite the improved responsiveness to primary therapy, survival of glioma patients is still very low. Therapies of malignant gliomas are often palliative because of their infiltrating nature and high recurrence. During the last decade, the concept that gliomas may arise from cancer stem cells (CSCs) has emerged. CSCs share with neural stem cells (NSCs) the capacity of cell renewal, multipotency and the expression of specific proteins, such as CD133 and nestin. This chapter describes similarities and differences between NSCs and CSCs, and summarizes the emerging knowledge on the possible role of stem cell markers as markers in gliomas, particularly in their tumoral grading. In addition, the importance of specific niches in maintaining pools of CSCs is considered. The involvement of signal transduction pathways, such as Notch, PDGF/PDGFR, Hedgehog-Gli1, and Bone morphogenetic protein and their implications in the control of CSCs function in gliomas are analyzed. Furthermore, certain proteins expressed in tumor migrating cells and possibly involved in recidive are evaluated.

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

  • Andreu-Agullò C, Morante-Redolat JM, Delgado AC, Farinas I (2009) Vascular niche factor PEDF modulates notch-dependent stemness in the adult subependymal zone. Nat Neurosci 12:1514–1523

    Article  PubMed  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 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Chen HL, Panchision DM (2007) Concise review: bone morphogenetic protein pleiotropism in neural stem cells and their derivatives–alternative pathways, convergent signals. Stem Cells 25:63–68

    Article  PubMed  CAS  Google Scholar 

  • Clement V, Sanchez P, de Tribolet N, Radovanovic I, Altaba RA (2007) HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal and tumorigenicity. Curr Biol 17:165–172

    Article  PubMed  CAS  Google Scholar 

  • Dahlstrand J, Collins VP, Lendahl U (1992) Expression of the class VI intermediate filament nestin in human central nervous system tumors. Cancer Res 52:5334–5341

    PubMed  CAS  Google Scholar 

  • do Carmo A, Patricio I, Cruz MT, Carvalheiro H, Oliveira CR, Lopes MC (2010) CXCL12/CXCR4 promotes motility and proliferation of glioma cells. Cancer Biol Ther 9:56–65

    Article  PubMed  CAS  Google Scholar 

  • Doyle LA, Ross DD (2003) Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2). Oncogene 22:7340–7358

    Article  PubMed  Google Scholar 

  • Ehtesham M, Winston JA, Kabos P, Thompson RC (2006) CXCR4 expression mediates glioma cell invasiveness. Oncogene 25:2801–2806

    Article  PubMed  CAS  Google Scholar 

  • Fan X, Matsui W, Khaki L, Stearns D, Chun J, Li YM, Eberhart CG (2006) Notch pathway inhibition depletes stem-like cells and blocks engraftment in embryonal brain tumors. Cancer Res 66:7445–7452

    Article  PubMed  CAS  Google Scholar 

  • Gangemi RM, Griffero F, Marubbi D, Perera M, Capra MC, Malatesta P, Ravetti GL, Zona GL, Daga A, Corte G (2009) SOX2 silencing in glioblastoma tumor-initiating cells causes stop of proliferation and loss of tumorigenicity. Stem Cells 27:40–48

    Article  PubMed  CAS  Google Scholar 

  • Gritti A, Vescovi AL, Galli R (2002) Adult neural stem cells: plasticity and developmental potential. J Physiol 96:81–90

    CAS  Google Scholar 

  • Hirschmann-Jax C, Foster AE, Wulf GG, Nuchtern JG, Jax TW, Gobel U, Goodell MA, Brenner MK (2004) A distinct “side population” of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci USA 101:14228–14233

    Article  PubMed  CAS  Google Scholar 

  • Holmin S, Almqvist P, Lendahl U, Mathiesen T (1997) Adult nestin-expressing subependymal cells differentiate to astrocytes in response to brain injury. Eur J Neurosci 9:65–75

    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 

  • Jackson EL, Garcia-Verdugo JM, Gil-Perotin S, Roy M, Quinones-Hinojosa A, VandenBerg S, Alvarez-Buylla A (2006) PDGFRα-positive B cells are neural stem cells in the adult SVZ that form glioma-like growths in response to increased PDGF signalling. Neuron 51:187–199

    Article  PubMed  CAS  Google Scholar 

  • Kania G, Corbeil D, Fuchs J, Tarasov KV, Blyszczuk P, Huttner WB, Boheler KR, Wobus am (2005) Somatic stem cell marker prominin-1/CD133 is expressed in embryonic stem cell-derived progenitors. Stem Cells 23:791–804

    Google Scholar 

  • Le Bras B, Barallobre MJ, Homman-Ludiye J, Ny A, Wyns S, Tammela T, Haiko P, Karkkainen MJ, Yuan L, Muriel MP, Chatzopoulou E, Bréant C, Zalc B, Carmeliet P, Alitalo K, Eichmann A, Thomas JL (2006) VEGF-C is a trophic factor for neural progenitors in the vertebrate embryonic brain. Nat Neurosci 9:340–348

    Article  PubMed  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 5:67–78

    Article  PubMed  Google Scholar 

  • Lokker NA, Sullivan CM, Hollenbach SJ, Israel MA, Giese NA (2002) Platelet-derived growth factor (PDGF) autocrine signalling regulates survival and mitogenic pathways in glioblastoma cells: evidence that the novel PDGF-C and PDGF-D ligands May play a role in the development of brain tumors. Cancer Res 62:3729–3735

    PubMed  CAS  Google Scholar 

  • Lottaz C, Beier D, Meyer K, Kumar P, Hermann A, Schwarz J, Junker M, Oefner PJ, Bogdahn U, Wischhusen J, Spang R, Storch A, Beier CP (2010) Transcriptional profiles of CD133+ and CD133- glioblastoma-derived cancer stem cell lines suggest different cells of origin. Cancer Res 70:2030–2040

    Article  PubMed  CAS  Google Scholar 

  • Mellodew K, Suhr R, Uwanogho DA, Reuter I, Lendahl U, Hodges H, Price J (2004) Nestin expression is lost in a neural stem cell line through a mechanism involving the proteasome and notch signalling. Develop Brain Res 151:13–23

    Article  CAS  Google Scholar 

  • Mizutani K, Yoon K, Dang L, Tokunaga A, Gaiano N (2007) Differential notch signaling distinguishes neural stem cells from intermediate progenitors. Nature 449:351–355

    Article  PubMed  CAS  Google Scholar 

  • Piccirillo SGM, Vescovi AL (2007) Bone morphogenetic proteins regulate tumorigenicity in human glioblastoma stem cells. Ernst Schering Found Symp Proc 5:59–81

    Article  Google Scholar 

  • Purow BW, Haque RM, Noel MW, Su Q, Burdick MJ, Lee J, Sundaresan T, Pastorino S, Park JK, Mikolaenko I, Maric D, Eberhart CG, Fine HA (2005) Expression of notch-1 and its ligands, delta-like-1 and jagged-1, is critical for glioma cell survival and proliferation. Cancer Res 65:2353–2363

    Article  PubMed  CAS  Google Scholar 

  • Ramirez-Castillejo C, Sànchez-Sànchez F, Andreu-Agullò C, Ferròn SR, Aroca-Aguillar JD, Sànchez P, Mira E, Escribano J, Farinas I (2006) Pigment epithelium-derived factor is a niche signal for neural stem cell renewal. Nat Neurosci 9:331–339

    Article  PubMed  CAS  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 

  • 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 

  • Rivera AL, Pelloski CE, Gilbert MR, Colman H, De La Cruz C, Sulman EP, Bekele BN, Aldape KD (2010) MGMT promoter methylation is predictive of response to radiotherapy and prognostic in the absence of adjuvant alkylating chemotherapy for glioblastoma. Neurooncol 12:116–121

    CAS  Google Scholar 

  • Sakakibara S, Nakamura Y, Satoh H, Okano H (2001) RNA-binding protein musashi2: developmentally regulated expression in neural precursor cells and subpopulation of neurons in mammalian CNS. J Neurosci 21:8097–8107

    Google Scholar 

  • Schepers GE, Teasdale RD, Koopman P (2002) Twenty pairs of sox: extent, homology, and nomenclature of the mouse and human sox transcription factor gene families. Develop Cell 3:167–170

    Article  CAS  Google Scholar 

  • Schimmer AD (2004) Inhibitor of apoptosis proteins: translating basic knowledge into clinical practice. Cancer Res 64:7183–7190

    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 tumor initiating cells. Nature 432:396–401

    Article  PubMed  CAS  Google Scholar 

  • Strojnik T, Røsland GV, Sakariassen PO, Kavalar R, Lah T (2007) Neural stem cell markers, nestin and musashi proteins, in the progression of human glioma: correlation of nestin with prognosis of patient survival. Surg Neurol 68:133–143

    Article  PubMed  Google Scholar 

  • Teodorczyk M, Martin-Villalba A (2010) Sensing invasion: cell surface receptors driving spreading of glioblastoma. J Cell Physiol 222:1–10

    Article  PubMed  CAS  Google Scholar 

  • Veselska R, Kuglik P, Cejpek P, Svachova H, Neradil J, Loja T, Relichova J (2006) Nestin expression in the cell lines derived from glioblastoma multiforme. BMC Cancer 6:32–43

    Article  PubMed  Google Scholar 

  • Wang J, Sakariassen PØ, Tsinkalovsky O, Immervoll H, Bøe SO, Svendsen A, Prestegarden L, Røsland G, Thorsen F, Stuhr L, Molven A, Bjerkvig R, Enger PØ (2008) CD133 negative glioma cells form tumors in nude rats and give rise to CD133+ cells. Int J Cancer 122:761–768

    Article  PubMed  CAS  Google Scholar 

  • Yu SC, Bian XW (2009) Enrichment of cancer stem cells based on heterogeneity of invasiveness. Stem Cell Rev 5:66–71

    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 

  • Zhang Z, Wang X, Wang S (2008) Chemosensitization effects of simultaneous suppression of MDR1 and XIAP in multidrug resistant glioma cells. Med Oncol 25:367–373

    Article  PubMed  CAS  Google Scholar 

  • Zimmerman L, Parr B, Lendahl U, Cunningham M, McKay R, Gavin B, Mann J, Vassileva G, McMahon A (1994) Independent regulatory elements in the nestin gene direct transgene expression to neural stem cells or muscle precursors. Neuron 12:11–24

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Mr. Francesco Marino for his helpful work for figure editing.

Author information

Authors and Affiliations

  1. Department of Medicine, Italian National Research Council, Institute of Neurological Sciences, Section of Catania, Gaifami P., 18, 95126, Catania, Italy

    P. Dell’Albani, R. Pellitteri, E.M. Tricarichi, S. D’Antoni, A. Berretta & M.V. Catania

Authors
  1. P. Dell’Albani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Pellitteri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E.M. Tricarichi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. D’Antoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Berretta
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M.V. Catania
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P. Dell’Albani .

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

Dell’Albani, P., Pellitteri, R., Tricarichi, E., D’Antoni, S., Berretta, A., Catania, M. (2011). Markers of Stem Cells in Gliomas. 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_19

Download citation

  • DOI: https://doi.org/10.1007/978-94-007-0344-5_19

  • 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