title: A radial glia gene marker, fatty acid binding protein 7 (FABP7), is involved in proliferation and invasion of glioblastoma cells.
abstract: Glioblastoma multiforme (GBM) is among the most deadly cancers. A number of studies suggest that a fraction of tumor cells with stem cell features (Glioma Stem-like Cells, GSC) might be responsible for GBM recurrence and aggressiveness. GSC similarly to normal neural stem cells, can form neurospheres (NS) in vitro, and seem to mirror the genetic features of the original tumor better than glioma cells growing adherently in the presence of serum. Using cDNA microarray analysis we identified a number of relevant genes for glioma biology that are differentially expressed in adherent cells and neurospheres derived from the same tumor. Fatty acid-binding protein 7 (FABP7) was identified as one of the most highly expressed genes in NS compared to their adherent counterpart. We found that down-regulation of FABP7 expression in NS by small interfering RNAs significantly reduced cell proliferation and migration. We also evaluated the potential involvement of FABP7 in response to radiotherapy, as this treatment may cause increased tumor infiltration. Migration of irradiated NS was associated to increased expression of FABP7. In agreement with this, in vivo reduced tumorigenicity of GBM cells with down-regulated expression of FABP7 was associated to decreased expression of the migration marker doublecortin. Notably, we observed that PPAR antagonists affect FABP7 expression and decrease the migration capability of NS after irradiation. As a whole, the data emphasize the role of FABP7 expression in GBM migration and provide translational hints on the timing of treatment with anti-FABP7 agents like PPAR antagonists during GBM evolution.
authors.affiliation: Siena Biotech Spa, Siena, Italy. aderosa@sienabiotech.it
authors.forename: Antonella
authors.initials: A
authors.lastname: De Rosa
authors.forename: Serena
authors.initials: S
authors.lastname: Pellegatta
authors.forename: Marco
authors.initials: M
authors.lastname: Rossi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Tunici
authors.forename: Letizia
authors.initials: L
authors.lastname: Magnoni
authors.forename: Maria Carmela
authors.initials: MC
authors.lastname: Speranza
authors.forename: Federico
authors.initials: F
authors.lastname: Malusa
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Miragliotta
authors.forename: Elisa
authors.initials: E
authors.lastname: Mori
authors.forename: Gaetano
authors.initials: G
authors.lastname: Finocchiaro
authors.forename: Annette
authors.initials: A
authors.lastname: Bakker
mesh_terms: D024506:5' Flanking Region; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D016000:Cluster Analysis; D000071438:Fatty Acid-Binding Protein 7; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D053263:Gene Regulatory Networks; D020868:Gene Silencing; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D047492:Peroxisome Proliferator-Activated Receptors / Q000037:antagonists & inhibitors; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D002352:Carrier Proteins; C107608:FABP7 protein, human; D000071438:Fatty Acid-Binding Protein 7; D047492:Peroxisome Proliferator-Activated Receptors; D025521:Tumor Suppressor Proteins