title: 3D collagen type I matrix inhibits the antimigratory effect of doxorubicin.
abstract: BACKGROUND
  The cell microenvironment, especially extracellular matrix proteins, plays an important role in tumor cell response to chemotherapeutic drugs. The present study was designed to investigate whether this microenvironment can influence the antimigratory effect of an anthracycline drug, doxorubicin, when tumor cells are grown in a matrix of type I collagen, a three-dimensional (3D) context which simulates a natural microenvironment.
  
  
  METHODS
  To this purpose, we studied the migratory parameters, the integrin expression, and the activation state of focal adhesion kinase (FAK) and GTPase RhoA involved in the formation of focal adhesions and cell movement. These parameters were evaluated at non toxic concentrations which did not affect HT1080 cell proliferation.
  
  
  RESULTS
  We show that while doxorubicin decreased cell migration properties by 70% in conventional two-dimensional (2D) culture, this effect was completely abolished in a 3D one. Regarding the impact of doxorubicin on the focal adhesion complexes, unlike in 2D systems, the data indicated that the drug neither affected beta1 integrin expression nor the state of phosphorylation of FAK and RhoA.
  
  
  CONCLUSIONS
  This study suggests the lack of antiinvasive effect of doxorubicin in a 3D environment which is generally considered to better mimic the phenotypic behaviour of cells in vivo. Consistent with the previously shown resistance to the cytotoxic effect in a 3D context, our results highlight the importance of the matrix configuration on the tumor cell response to antiinvasive drugs.
authors: UMR CNRS/URCA n°6237, UFR Pharmacie, 51 rue Cognacq-Jay, 51096 Reims Cedex, France.
authors: Emilie
authors: E
authors: Millerot-Serrurot
authors: UMR CNRS/URCA n°6237, UFR Pharmacie, 51 rue Cognacq-Jay, 51096 Reims Cedex, France.
authors: Marie
authors: M
authors: Guilbert
authors: IRI - CNRS USR3078, Parc de la Haute Borne, 50 Avenue Halley, 59650 Villeneuve d'Ascq Cedex, France.
authors: Nicolas
authors: N
authors: Fourré
authors: UMR CNRS/URCA n°6237, UFR Pharmacie, 51 rue Cognacq-Jay, 51096 Reims Cedex, France.
authors: Wojciech
authors: W
authors: Witkowski
authors: UMR CNRS/URCA n°6237, UFR Pharmacie, 51 rue Cognacq-Jay, 51096 Reims Cedex, France.
authors: Georges
authors: G
authors: Said
authors: UMR CNRS/URCA n°6237, UFR Pharmacie, 51 rue Cognacq-Jay, 51096 Reims Cedex, France.
authors: Laurence
authors: L
authors: Van Gulick
authors: Plateforme Imagerie Cellulaire et Tissulaire, IFR 53, 51 rue Cognacq-Jay, 51096 Reims Cedex, France.
authors: Christine
authors: C
authors: Terryn
authors: INSERM UMRS 903, CHU Maison Blanche, 45 rue Cognacq-Jay, 51092 Reims Cedex, France.
authors: Jean-Marie
authors: JM
authors: Zahm
authors: UMR CNRS/URCA n°6237, UFR Pharmacie, 51 rue Cognacq-Jay, 51096 Reims Cedex, France.
authors: Roselyne
authors: R
authors: Garnotel
authors: UMR CNRS/URCA n°6237, UFR Pharmacie, 51 rue Cognacq-Jay, 51096 Reims Cedex, France.
authors: Pierre
authors: P
authors: Jeannesson