Role of Interleukin-1β in Radiation-Enhancement of MDA-MB-231 Breast Cancer Cell Invasion

The ability of radiation to increase the invasiveness of cancer cells is associated with the inflammatory response, which is induced in almost all irradiated patients. For breast cancer patients, elevated plasma levels of the inflammatory cytokine interleukin-1 beta (IL1 beta) persisted for a few weeks after completion of radiotherapy. The aim of this study was to determine whether IL1 beta is involved in the enhancement of breast cancer cell invasion induced by radiation. The role of IL1 beta was assessed with invasion chambers where irradiated fibroblasts were used as chemoattractant for the MDA-MB-231 breast cancer cells plated in the upper compartment. The ability of IL1 beta to stimulate the expression of cyclooxygenase-2 (COX-2) and biosynthesis of the prostaglandin E2 (PGE2) in MDA-MB-231 cells were also determined. Our results show that radiation-enhancement of MDA-MB-231 cell invasion was prevented with an anti-IL1 beta antibody. The production of IL1 beta was increased in irradiated fibroblasts, while the invasiveness of the MDA-MB-231 cells not exposed to irradiated fibroblasts was favored by adding this cytokine. Furthermore, addition of the COX-2 inhibitor NS-398 prevented the stimulation of cancer cell invasion induced either by irradiated fibroblasts or IL1 beta. We propose that the effect of IL1 beta on the invasiveness of the MDA-MB-231 cells involves elevation of matrix metalloproteinase-9 (MMP-9) production, induction of COX-2 expression and PGE2 biosynthesis. In conclusion, this study supports the involvement of IL1 beta in the radiation-enhancement of breast cancer cell invasion. (C) 2013 by Radiation Research Society