Brain fatty acid-binding protein and ω-3/ω-6 fatty acids: Mechanistic insight into the poor prognosis of malignant glioma cell migration

• Author(s) / Creator(s)

  • Godbout, Roseline
  • Mita, Raja
  • Field, Catherine J.
  • Beaulieu, Michael J.

• Malignant gliomas (MG) are highly infiltrative tumors that consistently recur despite aggressive treatment. Brain fatty acid-binding protein (FABP7), which binds docosahexaenoic acid (DHA) and arachidonic acid (AA), localizes to sites of tumor infiltration and is associated with a poor prognosis in MG. Manipulation of FABP7 expression in MG cell lines affects cell migration, suggesting a role for FABP7 in tumor infiltration and recurrence. Here, we show that DHA inhibits and AA stimulates migration in an FABP7-dependent manner in U87 MG cells. We demonstrate that DHA binds to and sequesters FABP7 to the nucleus, resulting in decreased cell migration. This anti-migratory effect is partially dependent on peroxisome proliferator-activated receptor γ, a DHA-activated transcription factor. Conversely, AA-bound FABP7 stimulates cell migration by activating cyclooxygenase-2 and reducing peroxisome proliferator-activated receptor γ levels. Our data provide mechanistic insight as to why FABP7 is associated with a poor prognosis in MG and suggest that relative levels of DHA and AA in the tumor environment can make a profound impact on tumor growth properties. We propose that FABP7 and its fatty acid ligands may be key therapeutic targets for controlling the dissemination of MG cells within the brain.

• Date created

  2010

• Subjects / Keywords

  • Fatty Acid-Binding Protein
  • Lipids
  • Lipid-binding Protein
  • Tumour
  • Cell Migration
  • Fatty acids
  • Malignant Glioma

• Type of Item

  Article (Published)

• DOI

  https://doi.org/10.7939/R3HT2GR44

• License

  © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.