Abstract
Neurofibromatosis type 1 (NF1) is a common genetic disorder of the nervous system resulting in neurofibromas and malignant peripheral nerve sheath tumors (MPNST). In this study, we report the modulation of murine and human MPNST cell growth by the fatty acids docosahexaenoic acid (DHA) and arachidonic acid (AA). DHA demonstrated a tendency to stimulate cell growth at low doses and induce apoptosis at high doses, paralleled by the activation of ERK and caspase-3. Furthermore, high-dose DHA reversed the stimulation of MPNST cell growth by a number of growth factors suggested to have a pathogenic effect in NF1 and inhibited MPNST growth in vivo. AA was found to have a reciprocal activity in vitro, stimulating MPNST cell growth at comparable concentrations and reducing DHA activation of ERK. These findings introduce fatty acids as a possible regulator of MPNST development in NF1 patients.
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Abbreviations
- AA:
-
arachidonic acid
- DHA:
-
docosahexaenoic acid
- FABP:
-
fatty acid binding protein
- MPNST:
-
malignant peripheral nerve sheath tumor
- NF1:
-
neurofibromatosis type
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Acknowledgements
We would like to thank Dorota Denkhaus and Otrud Schmidt of the University of Bonn, and Wenzheng Wang and Camille O'Donnell of MGH for technical assistance. This work was supported by the German Fulbright Commission (GAM), the BONFOR research program of the University of Bonn (AKR and GAM), NIH Grant NS37895 (AK) and the Deutsche Krebshilfe No. 70-2635-Ma 3, 70-2794-De (SF and VFM).
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Mashour, G., Drissel, S., Frahm, S. et al. Differential modulation of malignant peripheral nerve sheath tumor growth by omega-3 and omega-6 fatty acids. Oncogene 24, 2367–2374 (2005). https://doi.org/10.1038/sj.onc.1208425
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DOI: https://doi.org/10.1038/sj.onc.1208425