gms | German Medical Science

Objective: The genetic and molecular events underlying glioma progression and growth have remained obscure. Recently, we have identified the receptor tyrosine kinase Axl as a novel mediator of glioma cell migration and invasion. Inhibition of Axl signaling resulted in a suppressed tumor growth and reduced tumor invasion in mice. To further study the relevance of Axl for glioma progression we have analyzed its expression in human tumor specimens.

Methods: Axl expression was analysed in n=20 high-grade glioma (all glioblastoma multiforme), 5 low-grade glioma (all astrocytoma WHO grade II), and 2 non-neoplastic brain specimens by means of RT-PCR, quantitative PCR (q-PCR), immunohistochemistry and western blotting.

Results: RT-PCR revealed a low-level baseline expression of Axl already in normal brain samples. q-PCR demonstrated stepwise upregulation of Axl expression in low grade glioma (2-fold increase when compared to normal brain) and high-grade glioma (up to 4-fold increase when compared to normal brain). Immunohistochemistry and western blotting confirmed elevated Axl expression in neoplastic tissue on the protein level.

Conclusions: Axl expression correlates with an increased malignancy of astroglial tumors, supporting a novel role for Axl in mediating glioma progression and growth. Specific targeting of Axl may represent a novel strategy to intervene with glioma growth and progression.