Article
The Trk-receptor inhibitor K-252a inhibits migration and invasion in human anaplastic oligodendroglomas
K-252a hemmt in humanen anaplastischen Oligodendrogliomen das Invasions- und Migrationsverhalten
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Published: | May 4, 2005 |
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Outline
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Objective
Neurotrophines are a family of polypeptides that regulate proliferation and differentiation in the CNS. The potential role of neurotrophic factors in human glial tissues and glial tumors is still not clear. We have investigated the expression of neurotrophic receptors in 10 human anaplastic oligodendrogliomas, the biological effects of NT-3, BDNF, and K-252a, a Trk-receptor inhibitor of neurotrophic factors, was analysed in 10 anaplastic oligodendroglomas.
Methods
The expression of neurotrophic factors receptors TrkC and TrkB was analyzed by immunohistochemistry and RT-PCR. Primary cell cultures human anaplastic oligodendrogliomas were treated with NT3, BDNF and K-252a (50ng/ml, 50ng/ml, and 100 nM). Migration was determined by using a videomorphometry-system. Invasion was investigated by three-dimensional collagen gels.
Results
The investigated oligodendrogliomas showed a different expression of neurotrophic factors receptors. Four oligodendrogliomas showed no or weak expression of TrkC and TrkB. The oligodendrogliomas found positiv for TrkB and TrkC showed heterogenous effects after treatment with NT-3, BDNF. In all the tumors investigated the treatment with K-252a displayed a less aggressive invasion pattern (up to 49%) and reduced migration (up to 67%).
Conclusions
Our data indicate that human anaplastic oligodendrogliomas have a heterogenous expression of neurotrophic factors receptors. The treated anaplastic oligodendrogliomas showed only heterogeneous biological effects after external treatment with neurotrophic factors. The treatment with the Trk-receptor inhibitor K-252a led to a significant increase of migration and invasion behaviour in human anaplastic oligodendrogliomas investigated. K-252a may be an agent in the treatment of these tumors.