1. ¹Children's Cancer Centre, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria 3052, Australia
2. ²Department of Paediatrics, University of Melbourne, Parkville, Victoria 3010, Australia
3. ³Department of Biochemistry, La Trobe University, Bundoora, Victoria 3086, Australia
4. ⁴Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA
5. ⁵Department of Surgery, University of Melbourne, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia
6. ⁶Oncogenic Signalling Laboratory and Tumor Targeting Program, Ludwig Institute for Cancer Research, Heidelberg, Victoria 3084, Australia
7. ⁷Department of Pathology, Molecular Pathology Research and Development Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria 8006, Australia
8. ⁸Department of Pathology, University of Melbourne, Parkville, Victoria 3010, Australia

Correspondence: Dr CJ Hawkins, Department of Biochemistry, La Trobe University, Bundoora, Victoria 3086, Australia. E-mail: c.hawkins@latrobe.edu.au

Received 12 May 2008; Accepted 12 May 2008; Published online 1 July 2008.

Abstract

TRAIL/Apo-2L has shown promise as an anti-glioma drug, based on investigations of TRAIL sensitivity in established glioma cell lines, but it is not known how accurately TRAIL signalling pathways of glioma cells in vivo are reproduced in these cell lines in vitro. To replicate as closely as possible the in vivo behaviour of malignant glioma cells, 17 early passage glioma cell lines and 5 freshly resected gliomas were exposed to TRAIL-based agents and/or chemotherapeutic drugs. Normal human hepatocytes and astrocytes and established glioma cell lines were also tested. Cross-linked TRAIL, but not soluble TRAIL, killed both normal cell types and cells from three tumours. Cells from only one glioma were killed by soluble TRAIL, although only inefficiently. High concentrations of cisplatin were lethal to glioma cells, hepatocytes and astrocytes. Isolated combinations of TRAIL and chemotherapy drugs were more toxic to particular gliomas than normal cells, but no combination was generally selective for glioma cells. This study highlights the widespread resistance of glioma cells to TRAIL-based agents, but suggests that a minority of high-grade glioma patients may benefit from particular combinations of TRAIL and chemotherapy drugs. In vitro sensitivity assays may help identify effective drug combinations for individual glioma patients.