Skip to main content
SpringerLink
Log in
Book cover

CNS Cancer pp 227–241Cite as

The Murine GL261 Glioma Experimental Model to Assess Novel Brain Tumor Treatments

  • Chapter
  • First Online:

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

The GL261 glioma is representative of a carcinogen-induced mouse syngeneic glioma model. This model represents one of the very few brain tumor models developed in immunocompetent animals that has growth characteristics similar to human GBM. The ideal animal model should share the invasive properties that the human GBM displays, since this is a major reason for the failure of current treatment strategies. Here we demonstrate, through a detailed comparison with human GBM, that the murine GL261 glioma closely mimics its human counterpart in a number of significant ways, but most importantly in its invasive and angiogenic properties representing the relevant biology of human GBMs. Therefore, it should prove to be a valuable preclinical model for testing novel drugs and therapeutic strategies that inhibit glioma invasion and angiogenesis.

This is a preview of subscription content, 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
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

Learn about institutional subscriptions

References

  • Abe T, Terada K, Wakimoto H, et al. (2003) PTEN decreases in vivo vascularization of experimental gliomas in spite of proangiogenic stimuli. Cancer Res 63:2300–2305

    PubMed  CAS  Google Scholar 

  • Ausman JI, Shapiro WR, Rall DP (1970) Studies on the chemotherapy of experimental brain tumors: development of an experimental model. Cancer Res 30:2394–2400

    PubMed  CAS  Google Scholar 

  • Brat DJ, Castellano-Sanchez AA, Hunter SB, et al. (2004) Pseudopalisades in glioblastoma are hypoxic, express extracellular matrix proteases, and are formed by an actively migrating cell population. Cancer Res 64:920–927

    Article  PubMed  CAS  Google Scholar 

  • Cha S, Johnson G, Wadghiri YZ, et al. (2003) Dynamic, contrast-enhanced perfusion MRI in mouse gliomas: correlation with histopathology. Magn Reson Med 49:848–855

    Article  PubMed  Google Scholar 

  • Choe G, Horvath S, Cloughesy TF, et al. (2003) Analysis of the phosphatidylinositol 3’-kinase signaling pathway in glioblastoma patients in vivo. Cancer Res 63:2742–2746

    PubMed  CAS  Google Scholar 

  • Davies MA, Lu Y, Sano T, et al. (1998) Adenoviral transgene expression of MMAC/PTEN in human glioma cells inhibits Akt activation and induces anoikis. Cancer Res 58:5285–5290

    PubMed  CAS  Google Scholar 

  • Ermoian RP, Furnis CS, Lamborn KR, et al. (2002) Dysregulation of PTEN and protein kinase B is associated with glioma histology and patient survival. Clin Cancer Res 8:1100–1106

    PubMed  CAS  Google Scholar 

  • Eshleman JS, Carlson BL, Mladek AC, et al. (2002) Inhibition of the mammalian target of rapamycin sensitizes U87 xenografts to fractionated radiation therapy. Cancer Res 62:7291–7297

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Forsythe JA, Jiang BH, Iyer NV, et al. (1996) Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol 16:4604–4613

    Google Scholar 

  • Glick RP, Lichtor T, de Zoeten E, et al. (1999) Prolongation of survival of mice with glioma treated with semiallogeneic fibroblasts secreting interleukin-2. Neurosurgery 45:867–874

    Article  PubMed  CAS  Google Scholar 

  • Heimberger AB, Crotty LE, Archer GE, et al. (2000) Bone marrow-derived dendritic cells pulsed with tumor homogenate induce immunity against syngeneic intracerebral glioma. J Neuroimmunol 103:16–25

    Article  PubMed  CAS  Google Scholar 

  • Heimberger AB, Learn CA, Archer GE, et al. (2002) Brain tumors in mice are susceptible to blockade of epidermal growth factor receptor (EGFR) with the oral, specific, EGFR-tyrosine kinase inhibitor ZD1839 (iressa). Clin Cancer Res 8:3496–3502

    PubMed  CAS  Google Scholar 

  • Hellums EK, Markert JM, Parker JN, et al. (2005) Increased efficacy of an interleukin-12 secreting herpes simplex virus in a syngeneic intracranial murine glioma model. Neuro-Oncol 7:213–224

    Article  PubMed  CAS  Google Scholar 

  • Hesselager G, Uhrbom L, Westermark B, et al. (2003) Complementary effects of platelet-derived growth factor autocrine stimulation and p53 or Ink4a-Arf deletion in a mouse glioma model. Cancer Res 63:4305–4309

    PubMed  CAS  Google Scholar 

  • Holash J, Maisonpierre PC, Compton D, et al. (1999) Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science 284:1994–1998

    Article  PubMed  CAS  Google Scholar 

  • Holland EC, Celestino J, Dai C, et al. (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 

  • Hu B, Guo P, Fang Q, et al. (2003) Angiopoietin-2 induces human glioma invasion through the activation of matrix metalloprotease-2. Proc Natl Acad Sci 100:8904–8909

    Article  PubMed  CAS  Google Scholar 

  • Hu B, Jarzynka MJ, Guo P, et al. (2006) Angiopoietin 2 induces glioma cell invasion by stimulating matrix metalloprotease 2 expression through the alphavbeta1 integrin and focal adhesion kinase signaling pathway. Cancer Res 66:775–783

    Article  PubMed  CAS  Google Scholar 

  • Kjaergaard J, Tanaka J, Kim JA, et al. (2000) Therapeutic efficacy of OX-40 receptor antibody depends on tumor immunogenicity and anatomic site of tumor growth. Cancer Res 60:5514–5521

    PubMed  CAS  Google Scholar 

  • Krishnamachary B, Berg-Dixon S, Kelly B, et al. (2003) Regulation of colon carcinoma cell invasion by hypoxia-inducible factor 1. Cancer Res 63:1138–1143

    PubMed  CAS  Google Scholar 

  • Learn CA, Grossi PM, Schmittling RJ, et al. (2007) Genetic analysis of intracranial tumors in a murine model of glioma demonstrate a shift in gene expression in response to host immunity. J Neuroimmunol 182:63–72

    Article  PubMed  CAS  Google Scholar 

  • Lumniczky K, Desaknai S, Mangel L, et al. (2002) Local tumor irradiation augments the antitumor effect of cytokine-producing autologous cancer cell vaccines in a murine glioma model. Cancer Gene Ther 9:44–52

    Article  PubMed  CAS  Google Scholar 

  • Martinez-Murillo R and Martinez A. (2007) Standardization of an orthotopic mouse brain tumor model following transplantation of CT-2A astrocytoma cells. Histol Histopathol 22:1309–1326

    PubMed  CAS  Google Scholar 

  • Miller CR, Williams CR, Buchsbaum DJ, et al. (2002) Intratumoral 5-fluorouracil produced by cytosine deaminase/5-flurocytosine gene therapy is effective for experimental human glioblastomas. Cancer Res 62:773–780

    PubMed  CAS  Google Scholar 

  • Miyatake S, Martuza RL, Rabkin SD (1997) Defective herpes simplex virus vectors expressing thymidine kinase for the treatment of malignant glioma. Cancer Gene Ther 4:222–228

    PubMed  CAS  Google Scholar 

  • Mohanam S, Cvhandrasekar N, Yanamandra N, et al. (2002) Modulation of invasive properties of human glioblastoma cells stably expressing amino-terminal fragment of urokinase-type plasminogen activator. Oncogene 21:7824–7830

    Article  PubMed  CAS  Google Scholar 

  • Nelson SJ, Cha S (2003) Imaging Glioblastoma Multiforme. Cancer J 9:134–145

    Article  PubMed  CAS  Google Scholar 

  • Newcomb EW, Tamasdan C, Entzminger Y, et al. (2004) Flavopiridol inhibits the growth of GL261 gliomas in vivo: Implications for malignant glioma therapy. Cell Cycle 3:230–234

    Article  PubMed  CAS  Google Scholar 

  • Newcomb EW, Demaria S, Lukyanov Y, et al. (2006) The combination of ionizing radiation and peripheral vaccination produces long-term survival of mice bearing established invasive GL261 tumors. Clin Cancer Res 12:4730–4737

    Article  PubMed  CAS  Google Scholar 

  • Peterson DL, Sheridan PJ, Brown WE, Jr. (1994) Animal models for brain tumors: historical perspectives and future directions. J Neurosurg 80:865–876

    Article  PubMed  CAS  Google Scholar 

  • Pichiule P, Chavez JC, LaManna JC. (2004) Hypoxic regulation of angiopoietin-2 expression in endothelial cells. J Biol Chem 279:12171–12180

    Article  PubMed  CAS  Google Scholar 

  • Plate KH, Breier G, Weich HA, et al. (1992) Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature 359:845–848

    Google Scholar 

  • Plautz GE, Touhalisky JE, Shu S. (1997) Treatment of murine gliomas by adoptive transfer ex vivo activated tumor-draining lymph node cells. Cell Immunol 178:101–107

    Article  PubMed  CAS  Google Scholar 

  • Reilly KM, Loisel DA, Bronson RT, et al. (2000) Nf1;Trp53 mutant mice develop glioblastoma with evidence of strain-specific effects. Nat Genet 26:109–113

    Article  PubMed  CAS  Google Scholar 

  • Reilly KM, Jacks T (2001) Genetically engineered mouse models of astrocytoma: GEMs in the rough? Semin Cancer Biol 11:177–190

    Article  PubMed  CAS  Google Scholar 

  • Sampson JN, Ashley DM, Archer GE, et al. (1997) Characterization of a spontaneous murine astrocytoma and abrogation of its tumorigenicity by cytokine secretion. Neurosurgery 41:1365–1372

    Google Scholar 

  • Scheid MN, Woodgett Jr (2003) Unraveling the activation mechanisms of protein kinase B/Akt. FEBS Letts 546:108–112

    Google Scholar 

  • Schold SC, Jr., Bigner DD (1983) A review of animal brain tumor models that have been used for therapeutic studies. In Walker MD ed. Oncology of the Nervous System. Boston: Nijhoff. p.31–63

    Chapter  Google Scholar 

  • Seligman AM, Shear MJ (1939) Studies in carcinogenesis. VIII. Experimental production of brain tumors in mice with methylcholanthrene. Am J Cancer 37:364–395

    CAS  Google Scholar 

  • Serano RD, Pegram CN, Bigner DD. (1980) Tumorigenic cell culture lines from a spontaneous VM/Dk murine astrocytoma (SMA). Acta Neuropathol 51:53–64

    Article  PubMed  CAS  Google Scholar 

  • Shweiki D, Itin A, Soffer D, et al. (1992) Vasular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 359:843–845

    Google Scholar 

  • Vivanco I, Sawyers CL (2002) The phosphatidylinositol 3-kinase-Akt pathway in human cancer. Nature Rev Cancer 2:489–501

    Article  CAS  Google Scholar 

  • Weiner NE, Pyles RB, Chalk CL, et al. (1999) A syngeneic mouse glioma model for study of glioblastoma therapy. J Neuropathol Exp Neurol 58:54–60

    Article  PubMed  CAS  Google Scholar 

  • Weiss WA, Israel M, Cobbs C, et al. (2002) Neuropathology of genetically engineered mice: consensus report and recommendations from an international forum. Oncogene 21:7453–7463

    Article  PubMed  CAS  Google Scholar 

  • Weissenberger J, Steinbach JP, Malin G, et al. (1997) Development and malignant progression of astrocytomas in GFAP-v-src transgenic mice. Oncogene 14:2005–2013

    Article  PubMed  CAS  Google Scholar 

  • Wiranowska M, Tresser N, Saporta S (1998) The effect of interferon and anti-CD44 antibody on mouse glioma invasiveness in vitro. Anticancer Res 18:3331–3338

    PubMed  CAS  Google Scholar 

  • Xiao A, Wu H, Pandolfi PP, et al. (2002) Astrocyte inactivation of the pRb pathway predisposes mice to malignant astrocytoma development that is accelerated by PTEN mutation. Cancer Cell 1:157–168

    Article  PubMed  CAS  Google Scholar 

  • Yu JS, Burwick JA, Dranoff G, et al. (1997) Gene therapy for metastatic brain tumors by vaccination with granulocyte-macrophage colony-stimulating factor-transduced tumor cells. Hum Gene Ther 8:1065–1072

    Article  PubMed  CAS  Google Scholar 

  • Zagzag D, Zhong H, Scalzitti JM, et al. (2000a) Expression of hypoxia-inducible factor 1α in human brain tumors: Association with angiogenesis, invasion and progression. Cancer 88:2606–2618

    Article  PubMed  CAS  Google Scholar 

  • Zagzag D, Amirnovin R, Greco MA, et al. (2000b) Vascular apoptosis and involution in gliomas precede neovascularization: A novel concept for glioma growth and angiogenesis. Lab Invest 80:837–849

    PubMed  CAS  Google Scholar 

  • Zagzag D, Miller DC, Chiriboga L, Yee H, et al. (2003) Green fluorescent protein immunohistochemistry as a novel experimental tool for the detection of glioma cell invasion in vivo. Brain Pathol 13:34–37

    Article  PubMed  Google Scholar 

  • Zagzag D, Lukyanov Y, Lan L, et al. (2006) Hypoxia-inducible factor-1 and VEGF upregulate CXCR4 in glioblastoma: implications for angiogenesis and glioma cell invasion. Lab Invest 86:1221–1232

    Article  PubMed  CAS  Google Scholar 

  • Zagzag D, Esencay M, Mendez O, et al. (2008) Hypoxia- and vascular endothelial growth factor-induced stromal cell-derived factor-1alpha/CXCR4 expression in glioblastomas: one plausible explanation of Scherer's structures. Am J Pathol 173:545–560

    Article  PubMed  CAS  Google Scholar 

  • Zimmerman H, Arnold H. (1941) Experimental brain tumors. I. Tumors produced with methylcholanthrene. Cancer Res 1:919–938

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, New York University Cancer Institute, New York University School of Medicine, New York, NY 10016, USA

    Elizabeth W. Newcomb & David Zagzag

Authors
  1. Elizabeth W. Newcomb
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David Zagzag
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elizabeth W. Newcomb .

Editor information

Editors and Affiliations

  1. School of Medicine, Emory University, Clifton Road 1365C, Atlanta, 30322, U.S.A.

    Erwin G. Meir

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Humana Press, a part of Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Newcomb, E.W., Zagzag, D. (2009). The Murine GL261 Glioma Experimental Model to Assess Novel Brain Tumor Treatments. In: Meir, E. (eds) CNS Cancer. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-60327-553-8_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-60327-553-8_12

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-60327-552-1

  • Online ISBN: 978-1-60327-553-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation