Article
EphrinB1 and EphB-receptor expression in human malignant gliomas and low grade astrocytomas
EphrinB1 und EphB-Rezeptor Expression in humanen malignen Gliomen und niedriggradigen Astrozytomen
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Published: | May 4, 2005 |
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Outline
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Objective
The involvement of receptor tyrosine kinases in tumor progression and differentiation is known in many tumor entities including those arising from brain tissue. The largest known family of receptor tyrosine kinases and their ligands is the Eph/Ephrin family. There is increasing evidence for up- or downregulation of certain Eph/Ephrin members in many different tumor types. Regarding Eph/Ephrin expression in human brain tumors only sparse data is available so far.
Methods
Gene expression profiling experiments revealed a differential expression of EphrinB1 mRNA in human GBM tissue compared with normal brain tissue. To further elucidate these findings we examined the mRNA expression of EphrinB1 and its receptors EphB1, EphB2 and EphB3 in GBM cell lines and tumor tissue by quantitative real time PCR. To compare gene expression at the protein level we performed western blot analyses.
Results
Mean gene expression in 10 human GBM specimens normalized to normal human brain were: 1.9 for EphrinB1, 0.8 for EphB1, 2.1 for EphB2 and 1.5 for EphB3. Mean results in 4 different malignant astrocytomas (WHO˚III) were: 2.7 for EphrinB1, 4.4 for EphB1, 2.6 for EphB2 and 2.0 for EphB3. In 3 low grade astrocytomas (LGAs) WHO˚II we measured: 1.6 for EphrinB1, 6.4 for EphB1, 1.5 for EphB2 and 2.5 for EphB3. We analyzed 15 GBM specimens and 4 LGAs (WHO˚II) by western blot and were able to detect EphrinB1 protein in 80% of the GBMs. All LGAs expressed EphrinB1 protein. EphB1 protein was found in 75% of the GBMs. All LGAs were positive. EphB2 was detected in 50% of the GBM samples. In 25% of the LGAs EphB2 protein was not detectable. EphB3 protein could be found reliable in 50% of the GBMs and in 50% of the LGAs.
Conclusions
In Conclusion our results show an expression of EphrinB1 and all of its receptors on mRNA and protein level in normal human brain tissue, low grade astrocytomas and malignant gliomas. Human GBMs and malignant astrocytomas overexpressed EphrinB1 and EphB2 mRNA. EphB1 is overexpressed in malignant astrocytomas but not in GBMs. In low grade astrocytomas an overexpression of EphB1 and EphB3 mRNA is detectable. In future experiments functional studies with inhibitory ligands and antibodies will be performed and may lead to a deeper understanding of glioma progression mechanisms thus helping to find possible targets for new treatment approaches.