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-1β (IL1β) persisted for a few weeks after completion of
radiotherapy. The aim of this study was to determine whether IL1β is involved in the enhancement of
breast cancer cell invasion induced by radiation. The role of IL1β 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 IL1β 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-IL1β antibody. The production of IL1β 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 IL1β. We propose that the effect of IL1β 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 IL1β in the radiation-enhancement of
breast cancer cell invasion.