Journal of Neuro-Oncology

, Volume 95, Issue 1, pp 13–22

Glioma-associated endothelial cells are chemoresistant to temozolomide

  • Jenilyn J. Virrey
  • Encouse B. Golden
  • Walavan Sivakumar
  • Weijun Wang
  • Ligaya Pen
  • Axel H. Schönthal
  • Florence M. Hofman
  • Thomas C. Chen
Laboratory Investigation - Human/animal tissue

Abstract

Temozolomide is considered the standard of care and drug of choice for the treatment of initially diagnosed malignant gliomas. Although well tolerated, temozolomide still has limited clinical efficacy. Following drug treatment, patient prognosis still remains poor; tumor recurrence is almost universal. We hypothesized that this lack of effectiveness with temozolomide is because this drug does not target the glioma microenvironment, which is highly vascular in malignant gliomas. To test this hypothesis we analyzed the effects of temozolomide on the tumor vasculature in vitro and in vivo. We found that this drug did not affect the viability or proliferation rate of endothelial cells isolated from human glioma specimens, although temozolomide was highly cytotoxic to the glioma cell lines U87MG and U251. Furthermore, temozolomide did not inhibit the migration of these glioma-associated endothelial cells, a key mechanism responsible for tumor angiogenesis. In in vivo studies, using the intracranial glioma mouse model, temozolomide did not cause a pronounced effect on microvessel density. Our findings show that temozolomide has no apparent effect on the glioma vascular microenvironment. Thus combination therapy with anti-vascular agents may enhance temozolomide effectiveness as glioma therapeutic protocol.

Keywords

Temozolomide Endothelial cells Glioblastoma multiforme Angiogenesis 

Supplementary material

11060_2009_9891_MOESM1_ESM.doc (48 kb)
Supplementary material 1 (DOC 49 kb)

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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Jenilyn J. Virrey
    • 1
  • Encouse B. Golden
    • 1
  • Walavan Sivakumar
    • 2
  • Weijun Wang
    • 2
  • Ligaya Pen
    • 1
  • Axel H. Schönthal
    • 3
  • Florence M. Hofman
    • 1
  • Thomas C. Chen
    • 1
    • 4
  1. 1.Departments of PathologyKeck School of Medicine, University of Southern CaliforniaLos AngelesUSA
  2. 2.Departments of NeurosurgeryKeck School of Medicine, University of Southern CaliforniaLos AngelesUSA
  3. 3.Departments of Microbiology and ImmunologyKeck School of Medicine, University of Southern CaliforniaLos AngelesUSA
  4. 4.Los AngelesUSA

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