title: Temozolomide modifies caveolin-1 expression in experimental malignant gliomas in vitro and in vivo.
abstract: BACKGROUND
  Caveolin-1 is a protein that displays promotive versus preventive roles in cancer progression according to circumstances. Temozolomide (TMZ) is the standard chemotherapeutic to treat glioma patients. The present work aims to characterizeTMZ-induced effects on caveolin-1 expression in glioma cells.
  
  
  METHODS
  Human astroglioma (U373 and T98G) and oligodendroglioma (Hs683) cell lines were used in vitro as well as in vivo orthotopic xenografts (Hs683 and U373) into the brains of immunocompromisedmice. In vitro TMZ-induced effects on protein expression and cellular localization were determined by Western blot analysis and on the actin cytoskeleton organization by means of immunofluorescence approaches. In vivo TMZ-induced effects in caveolin-1 expression in human glioma xenografts were monitored by means of immunohistochemistry.
  
  
  RESULTS
  TMZ modified caveolin-1 expression and localization in vitro and in vivo after an administration schedule that slightly, if at all, impaired cell growth characteristics in vitro. Caveolin-1 by itself (at a 100-ng/ml concentration) was able to significantly reduce invasiveness (Boyden chambers) of the three human glioma cell lines. The TMZ-inducedmodification in caveolin-1 expression in flotation/raft compartments was paralleled by altered Cyr61 and β(1) integrin expression, two elements that have already been reported to collaborate with caveolin-1 in regulating glioma cell biology, and all these features led to profound reorganization of the actin cytoskeleton. An experimental Src kinase inhibitor, AZD0530, almost completely antagonized the TMZ-induced modulation in caveolin-1 expression.
  
  
  CONCLUSIONS
  TMZ modifies caveolin-1 expression in vitro and in vivo in glioma cells, a feature that directly affects glioma cell migration properties.
authors: Laboratoire de Toxicologie, Faculté de Pharmacie, Université Libre de Bruxelles, Brussels, Belgium.
authors: Céline
authors: C
authors: Bruyère
authors: Laurence
authors: L
authors: Abeloos
authors: Delphine
authors: D
authors: Lamoral-Theys
authors: Rebecca
authors: R
authors: Senetta
authors: Véronique
authors: V
authors: Mathieu
authors: Marie
authors: M
authors: Le Mercier
authors: Richard E
authors: RE
authors: Kast
authors: Paola
authors: P
authors: Cassoni
authors: Guy
authors: G
authors: Vandenbussche
authors: Robert
authors: R
authors: Kiss
authors: Florence
authors: F
authors: Lefranc