title: The 18 kDa translocator protein influences angiogenesis, as well as aggressiveness, adhesion, migration, and proliferation of glioblastoma cells.
abstract: BACKGROUND
  It is known that the mitochondrial 18 kDa translocator protein (TSPO) is present in almost all peripheral tissues and also in glial cells in the brain. TSPO levels are typically enhanced in correlation with tumorigenesis of cancer cells including glioblastoma. Relevant for angiogenesis, TSPO is also present in almost all cells of the cardiovascular system.
  
  
  METHODS
  We studied the effect of TSPO knockdown by siRNA on various aspects of tumor growth of U118MG glioblastoma cells in two in-vivo models: a nude mouse model with intracerebral implants of U118MG glioblastoma cells and implantation of U118MG glioblastoma cells on the chorionallantoic membrane (CAM) of chicken embryos. In vitro, we further assayed the influence of TSPO on the invasive potential of U118MG cells.
  
  
  RESULTS
  TSPO knockdown increased tumor growth in both in-vivo models compared with the scrambled siRNA control. Angiogenesis was also increased by TSPO knockdown as determined by a CAM assay. TSPO knockdown led to a decrease in adhesion to the proteins of the extracellular matrix, including fibronectin, collagen I, collagen IV, laminin I, and fibrinogen. TSPO knockdown also led to an enhancement in the migratory capability of U118MG cells, as determined in a modified Boyden chamber. Application of the TSPO ligand 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide (PK 11195) at a concentration of 25 µmol/l in the in-vitro models yielded results similar to those obtained on TSPO knockdown. We found no effects of PK 11195 on TSPO protein expression. Interestingly, at low nmol/l concentrations (around 1 nmol/l), PK 11195 enhanced adhesion to collagen I, suggesting a bimodal concentration effect of PK 11195.
  
  
  CONCLUSIONS
  Intact TSPO appears to be able to counteract the invasive and angiogenic characteristics related to the aggressiveness of U118MG glioblastoma cells in vivo and in vitro.
authors.affiliation: Department of Pediatrics I - Haematology/Oncology, University Medical Center, Göttingen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Bode
authors.forename: Leo
authors.initials: L
authors.lastname: Veenman
authors.forename: Beatriz
authors.initials: B
authors.lastname: Caballero
authors.forename: Max
authors.initials: M
authors.lastname: Lakomek
authors.forename: Wilfried
authors.initials: W
authors.lastname: Kugler
authors.forename: Moshe
authors.initials: M
authors.lastname: Gavish
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002642:Chick Embryo; D005909:Glioblastoma / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D008024:Ligands; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic; D034741:RNA, Small Interfering / Q000378:metabolism; D018079:Receptors, GABA / Q000378:metabolism*
chemical_list: D007546:Isoquinolines; D008024:Ligands; D034741:RNA, Small Interfering; D018079:Receptors, GABA; C499229:TSPO protein, human; C037850:PK 11195