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Cancer Cell International
Published in: Cancer Cell International 1/2010

Open Access 01-12-2010 | Primary research

3D collagen type I matrix inhibits the antimigratory effect of doxorubicin

Authors: Emilie Millerot-Serrurot, Marie Guilbert, Nicolas Fourré, Wojciech Witkowski, Georges Said, Laurence Van Gulick, Christine Terryn, Jean-Marie Zahm, Roselyne Garnotel, Pierre Jeannesson

Published in: Cancer Cell International | Issue 1/2010

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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 β1 integrin expression nor the state of phosphorylation of FAK and RhoA.

Conclusion

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.
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Metadata
Title
3D collagen type I matrix inhibits the antimigratory effect of doxorubicin
Authors
Emilie Millerot-Serrurot
Marie Guilbert
Nicolas Fourré
Wojciech Witkowski
Georges Said
Laurence Van Gulick
Christine Terryn
Jean-Marie Zahm
Roselyne Garnotel
Pierre Jeannesson
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2010
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/1475-2867-10-26

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