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.
Highlights
If cancer cells possess an intrinsic ability to grow and disseminate, increasing evidence suggests, that proliferative and invasive properties of cancer cells are acquired through exposure to paracrine signals that they receive from the surrounding microenvironment [1, 2]
We explored the mechanisms accounting for chemokine expression in mesenchymal stem cells (MSCs) by testing whether MDAMB-231 could induce in MSCs the NF-κB signaling, a known regulator of the expression of many chemokines
Incubation of the MSCs with the MDA-MB-231 conditioned medium (CM) led to p65 nuclear relocalization, in 33% of the cells in contrast to the MCF-7 CM that only raised the percentage of MSCs positive for nuclear p65 from 2% to 5% (Supplementary Figure S5B)
Summary
If cancer cells possess an intrinsic ability to grow and disseminate, increasing evidence suggests, that proliferative and invasive properties of cancer cells are acquired through exposure to paracrine signals that they receive from the surrounding microenvironment [1, 2]. The role of cells such as CAFs (carcinoma associated fibroblasts) has been highlighted [3, 4]. Mesenchymal stem cells (MSC) have been recently described as another source of CAFs in addition to fibroblasts [5,6,7]. MSCs have been isolated from bone marrow (BM), adipose tissue, peripheral blood, fetal liver, lung, amniotic fluid, chorionic villi of the placenta, and umbilical cord blood [4]. MSCs are capable of self-renewal and differentiation into several cell types such as chondrocytes, adipocytes, osteocytes and myocytes. The immuno-suppressive properties of MSCs have been in particular clinically exploited for graft-versus-host and autoimmune diseases [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
