Journal of Neuro-Oncology

, Volume 85, Issue 2, pp 133–148 | Cite as

Intracranial glioblastoma models in preclinical neuro-oncology: neuropathological characterization and tumor progression

  • Marianela Candolfi
  • James F. Curtin
  • W. Stephen Nichols
  • AKM. G. Muhammad
  • Gwendalyn D. King
  • G. Elizabeth Pluhar
  • Elizabeth A. McNiel
  • John R. Ohlfest
  • Andrew B. Freese
  • Peter F. Moore
  • Jonathan Lerner
  • Pedro R. Lowenstein
  • Maria G. Castro
Lab Investigation-Human/Animal Tissue

Abstract

Although rodent glioblastoma (GBM) models have been used for over 30 years, the extent to which they recapitulate the characteristics encountered in human GBMs remains controversial. We studied the histopathological features of dog GBM and human xenograft GBM models in immune-deficient mice (U251 and U87 GBM in nude Balb/c), and syngeneic GBMs in immune-competent rodents (GL26 cells in C57BL/6 mice, CNS-1 cells in Lewis rats). All GBMs studied exhibited neovascularization, pleomorphism, vimentin immunoreactivity, and infiltration of T-cells and macrophages. All the tumors showed necrosis and hemorrhages, except the U87 human xenograft, in which the most salient feature was its profuse neovascularization. The tumors differed in the expression of astrocytic intermediate filaments: human and dog GBMs, as well as U251 xenografts expressed glial fibrillary acidic protein (GFAP) and vimentin, while the U87 xenograft and the syngeneic rodent GBMs were GFAP and vimentin+. Also, only dog GBMs exhibited endothelial proliferation, a key feature that was absent in the murine models. In all spontaneous and implanted GBMs we found histopathological features compatible with tumor invasion into the non-neoplastic brain parenchyma. Our data indicate that murine models of GBM appear to recapitulate several of the human GBM histopathological features and, considering their reproducibility and availability, they constitute a valuable in vivo system for preclinical studies. Importantly, our results indicate that dog GBM emerges as an attractive animal model for testing novel therapies in a spontaneous tumor in the context of a larger brain.

Keywords

Glioma Dog U251 U87 CNS-1 GL26 

Notes

Acknowledgments

This work is supported by National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS) Grant 1R01 NS44556.01, Minority Supplement NS445561; 1R21-NSO54143.01; 1UO1 NS052465.01; NIH/NINDS 1 RO3 TW006273-01 to M.G.C.; NIH/NINDS Grants 1 RO1 NS 054193.01; RO1 NS 42893.01; U54 NS045309-01, and 1R21 NS047298-01 to P.R.L. The Bram and Elaine Goldsmith and the Medallions Group Endowed Chairs in Gene Therapeutics to PRL and MGC, respectively, The Linda Tallen and David Paul Kane Foundation Annual Fellowship and the Board of Governors at CSMC. M.C and GDK are supported by NIH/NINDS 1F32 NS058156.01 and 1F32 NS0503034.01.

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Marianela Candolfi
    • 1
    • 2
  • James F. Curtin
    • 1
    • 2
  • W. Stephen Nichols
    • 6
  • AKM. G. Muhammad
    • 1
  • Gwendalyn D. King
    • 1
    • 2
  • G. Elizabeth Pluhar
    • 3
  • Elizabeth A. McNiel
    • 3
  • John R. Ohlfest
    • 4
  • Andrew B. Freese
    • 4
  • Peter F. Moore
    • 5
  • Jonathan Lerner
    • 1
    • 2
  • Pedro R. Lowenstein
    • 1
    • 2
  • Maria G. Castro
    • 1
    • 2
  1. 1.Departments of Molecular and Medical Pharmacology and Medicine, David Geffen School of MedicineUCLALos AngelesUSA
  2. 2.Board of Governors’ Gene Therapeutics Research InstituteCedars-Sinai Medical CenterLos AngelesUSA
  3. 3.Department of Veterinary Clinical SciencesUniversity of MinnesotaSaint PaulUSA
  4. 4.Department of NeurosurgeryUniversity of MinnesotaMinneapolisUSA
  5. 5.Department of Veterinary, Pathology, Microbiology, and Immunology, School of Veterinary MedicineUniversity of CaliforniaDavisUSA
  6. 6.Department of Pathology and Laboratory MedicineCedars-Sinai Medical CenterLos AngelesUSA

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