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Journal of Neuro-Oncology

, Volume 90, Issue 2, pp 125–132 | Cite as

Tissue transgluaminase 2 expression in meningiomas

  • Liya Yuan
  • Amir Behdad
  • Matthew Siegel
  • Chaitan Khosla
  • Ryuji Higashikubo
  • Keith M. Rich
Lab. Investigation-human/animal tissue

Abstract

Meningiomas are common intracranial tumors that occur in extra-axial locations, most often over the cerebral convexities or along the skull-base. Although often histologically benign these tumors frequently present challenging clinical problems. Primary clinical management of patients with symptomatic tumors is surgical resection. Radiation treatment may arrest growth or delay recurrence of these tumors, however, meningioma cells are generally resistant to apoptosis after treatment with radiation. Tumor cells are known to alter their expression of proteins that interact in the ECM to provide signals important in tumor progression. One such protein, fibronectin, is expressed in elevated levels in the ECM in a number of tumors including meningiomas. We recently reported that levels of both extracellular fibronectin and tissue transglutaminase 2 (TG2) were increased in glioblastomas. We examined the expression of fibronectin and its association TG2 in meningiomas. Both fibronectin and TG2 were strongly expressed in all meningiomas studied. TG2 activity was markedly elevated in meningiomas, and TG2 was found to co-localize with fibronectin. Treatment of meningiomas with the small molecule TG2 inhibitor, KCC009, inhibited the binding of TG2 to fibronectin and blocked disposition of linear strands of fibronectin in the ECM. KCC009 treatment promoted apoptosis and enhanced radiation sensitivity both in cultured IOMM-Lee meningioma cells and in meningioma tumor explants. These findings support a potential protective role for TG2 in meningiomas.

Keywords

Brain tumor Cell death Tissue transglutaminase inhibitor Radiation 

Notes

Acknowledgments

This work is supported by a grant from the Barnes-Jewish Hospital (to K.M.R.) and by a Grant from the NIH (R01 DK63158 to C.K.). In accordance with Washington University financial disclosure policy, K.M.R. has a relationship with Alvine Pharmaceutical,Inc with regard to KCC009. M.S. is a recipient of a predoctoral fellowship from the Stanford-NIH Biotechnology Training Grant. We thank Dr. Mark Watson for assistance in sharing specimens from the Washington Tumor Repository.

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Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Liya Yuan
    • 1
  • Amir Behdad
    • 1
  • Matthew Siegel
    • 2
  • Chaitan Khosla
    • 2
  • Ryuji Higashikubo
    • 3
  • Keith M. Rich
    • 1
    • 3
    • 4
  1. 1.Department of Neurological SurgeryWashington University School of MedicineSt. LouisUSA
  2. 2.Departments of Chemistry and Chemical EngineeringStanford UniversityStanfordUSA
  3. 3.Department of Radiation OncologyWashington University School of MedicineSt. LouisUSA
  4. 4.Department of Anatomy and NeurobiologyWashington University School of MedicineSt. LouisUSA

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