Research Papers:

IL-1β produced by aggressive breast cancer cells is one of the factors that dictate their interactions with mesenchymal stem cells through chemokine production

Pauline Escobar _, Céline Bouclier, Julien Serret, Ivan Bièche, Madly Brigitte, Andres Caicedo, Elodie Sanchez, Sophie Vacher, Marie-Luce Vignais, Philippe Bourin, David Geneviève, Franck Molina, Christian Jorgensen and Gwendal Lazennec

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Oncotarget. 2015; 6:29034-29047. https://doi.org/10.18632/oncotarget.4732

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Pauline Escobar2,*, Céline Bouclier1,2,*, Julien Serret2, Ivan Bièche3, Madly Brigitte2, Andres Caicedo2, Elodie Sanchez2, Sophie Vacher3, Marie-Luce Vignais2, Philippe Bourin4,5, David Geneviève2, Franck Molina1, Christian Jorgensen2, Gwendal Lazennec1

1CNRS, SYS2DIAG, Cap Delta, Montpellier, F-34184, France

2INSERM, U844, U1183, Montpellier, F-34091, France

3Institut Curie, Unité de Pharmacogénomique, Département de Génétique, Paris, 75248, France

4Univercell Biosolutions, Pierre Potier, Toulouse, F-31106, France

5CSA21, Toulouse, F-31100, France

*These authors have contributed equally to this work

Correspondence to:

Gwendal Lazennec, e-mail: [email protected]

Keywords: breast, cancer, mesenchymal stem cells, IL-1beta, chemokines

Received: March 16, 2015     Accepted: July 22, 2015     Published: August 04, 2015


The aim of this work was to understand whether the nature of breast cancer cells could modify the nature of the dialog of mesenchymal stem cells (MSCs) with cancer cells. By treating MSCs with the conditioned medium of metastatic Estrogen-receptor (ER)-negative MDA-MB-231, or non-metastatic ER-positive MCF-7 breast cancer cells, we observed that a number of chemokines were produced at higher levels by MSCs treated with MDA-MB-231 conditioned medium (CM). MDA-MB-231 cells were able to induce NF-κB signaling in MSC cells. This was shown by the use of a NF-kB chemical inhibitor or an IκB dominant negative mutant, nuclear translocation of p65 and induction of NF-κB signature. Our results suggest that MDA-MB-231 cells exert their effects on MSCs through the secretion of IL-1β, that activates MSCs and induces the same chemokines as the MDA-MB-231CM. In addition, inhibition of IL-1β secretion in the MDA-MB-231 cells reduces the induced production of a panel of chemokines by MSCs, as well the motility of MDA-MB-231 cells. Our data suggest that aggressive breast cancer cells secrete IL-1β, which increases the production of chemokines by MSCs.

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