Overexpression of ADK in human astrocytic tumors and peritumoral tissue is related to tumor-associated epilepsy

Marjolein De Groot, Anand Iyer, Emanuele Zurolo, Jasper Anink, Jan J. Heimans, Detlev Boison, Jaap C. Reijneveld, Eleonora Aronica

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Purpose: Adenosine kinase (ADK), a largely astrocyte-based metabolic enzyme, regulates adenosine homeostasis in the brain. Overexpression of ADK decreases extracellular adenosine and consequently leads to seizures. We hypothesized that dysfunction in the metabolism of tumor astrocytes is related to changes in ADK expression and that those changes might be associated with the development of epilepsy in patients with tumors. Methods: We compared ADK expression and cellular distribution in surgically removed tumor tissue (n = 45) and peritumoral cortex (n = 20) of patients with glial and glioneuronal tumors to normal control tissue obtained at autopsy (n = 11). In addition, we compared ADK expression in tumor patients with and without epilepsy. To investigate ADK expression, we used immunohistochemistry and Western blot analysis. ADK activity measurement was performed in surgical specimens of astrocytomas World Health Organization (WHO) grade III (n = 3), peritumoral cortex (n = 3), and nonepileptic cortex (n = 3). Key Findings: Immunohistochemistry predominantly showed cytoplasmic labeling in tumors and peritumoral tissue containing infiltrating tumor cells. ADK immunoreactivity was significantly stronger in tumor and peritumoral tissue compared to normal white matter and normal cortex, especially in astrocytoma WHO grade III, as confirmed by Western blot analysis and ADK activity measurements. Importantly, we found a significantly higher expression of ADK in the peritumoral infiltrated tissue of patients with epilepsy than in patients without epilepsy. Significance: These results suggest a dysregulation of ADK in astrocytic brain tumors. Moreover, the upregulation of ADK observed in peritumoral infiltrated tissue of glioma patients with epilepsy supports the role of this enzyme in tumor-associated epilepsy.

Original languageEnglish (US)
Pages (from-to)58-66
Number of pages9
JournalEpilepsia
Volume53
Issue number1
DOIs
StatePublished - Jan 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Keywords

  • Adenosine kinase
  • Astrocytoma
  • Brain tumors
  • Epilepsy
  • Human
  • Peritumoral cortex

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