3D collagen type I matrix inhibits the antimigratory effect of doxorubicin.
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.
Millerot-Serrurot
Emilie
E
UMR CNRS/URCA n°6237, UFR Pharmacie, 51 rue Cognacq-Jay, 51096 Reims Cedex, France.
Guilbert
Marie
M
UMR CNRS/URCA n°6237, UFR Pharmacie, 51 rue Cognacq-Jay, 51096 Reims Cedex, France.
Fourré
Nicolas
N
IRI - CNRS USR3078, Parc de la Haute Borne, 50 Avenue Halley, 59650 Villeneuve d'Ascq Cedex, France.
Witkowski
Wojciech
W
UMR CNRS/URCA n°6237, UFR Pharmacie, 51 rue Cognacq-Jay, 51096 Reims Cedex, France.
Said
Georges
G
UMR CNRS/URCA n°6237, UFR Pharmacie, 51 rue Cognacq-Jay, 51096 Reims Cedex, France.
Van Gulick
Laurence
L
UMR CNRS/URCA n°6237, UFR Pharmacie, 51 rue Cognacq-Jay, 51096 Reims Cedex, France.
Terryn
Christine
C
Plateforme Imagerie Cellulaire et Tissulaire, IFR 53, 51 rue Cognacq-Jay, 51096 Reims Cedex, France.
Zahm
Jean-Marie
JM
INSERM UMRS 903, CHU Maison Blanche, 45 rue Cognacq-Jay, 51092 Reims Cedex, France.
Garnotel
Roselyne
R
UMR CNRS/URCA n°6237, UFR Pharmacie, 51 rue Cognacq-Jay, 51096 Reims Cedex, France.
Jeannesson
Pierre
P
UMR CNRS/URCA n°6237, UFR Pharmacie, 51 rue Cognacq-Jay, 51096 Reims Cedex, France.