IL-1β produced by aggressive breast cancer cells is one of the factors that dictate their interactions with mesenchymal stem cells through chemokine production
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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
Gwendal Lazennec, e-mail: email@example.com
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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