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, Gwendal Lazennec

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)29034-29047
Number of pages14
JournalOncotarget
Volume6
Issue number30
DOIs
StatePublished - 2015
Externally publishedYes

Keywords

  • Breast
  • Cancer
  • Chemokines
  • IL-1beta
  • Mesenchymal stem cells

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