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-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.
Center for Research In Radiotherapy, Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Science, Université de Sherbrooke, Sherbrooke, QC, Canada.
Benoit
B
Paquette
Hélène
H
Therriault
J Richard
JR
Wagner
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000502:physiology; D017931:DNA Primers; D015232:Dinoprostone / Q000096:biosynthesis; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D051379:Mice; D009361:Neoplasm Invasiveness
D017931:DNA Primers; D053583:Interleukin-1beta; D051546:Cyclooxygenase 2; D020780:Matrix Metalloproteinase 9; D015232:Dinoprostone