Role of the GAS6-AXL receptor-ligand pairing in migration of human glioma cells

James Smith, Geoff Pilkington, Sassan Hafizi

Research output: Contribution to journalArticlepeer-review

Abstract

INTRODUCTION: The Axl receptor tyrosine kinase (RTK) and its ligand Gas6, have previously been shown to regulate neoplastic cell motility, migration, invasion and proliferation. The aim of this study was to determine the role of Gas6/Axl on migration of human glioma cells. METHODS: Three human glioblastoma derived cell lines of differing origin and degree of heterogeneity,were screened for Axl protein expression by western blot. For investigation of cell migration, serum-starved cells were stimulated with recombinant human Gas6, and scratch wound assays coupled with live cell imaging were performed to monitor the migration rates of these cells. The cells were also analysed for intracellular signalling effects on Axl and phospho-Axl by western blot and protein tyrosine kinase assays. RESULTS: We detected expression of Axl protein in SNB-19 (homogeneous) and UPAB (heterogeneous) cell lines, although not in IN699 (paediatric). It was furthermore demonstrated that Gas6 stimulated the migration of SNB-19 cells over 36 h by a two-fold increase as compared to control-treated cells, resulting in a migration speed of 11.650+0.564 mm/h compared to 6.861+1.264 mm/h. Moreover, a Gas6 concentration-dependent response was observed, revealing a specific promotion of migration (p , 0.05). CONCLUSIONS: Stimulation of the Axl RTK with its ligand Gas6 stimulates migration of human glioma cells, a mechanism that remains to be fully understood. These data can help to understand the mechanisms of local invasion in brain tumours. We wish, therefore, to further investigate Axl activation as well as related signalling pathway activities in glioma cells to help understand the molecular basis of glioma migration and invasion.
Original languageEnglish
Pages (from-to)i9
JournalNeuro-Oncology
Volume12
Issue numberSupp 1
DOIs
Publication statusPublished - 2010

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