Center for Research In Radiotherapy, Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Science, Université de Sherbrooke, Sherbrooke, QC, Canada.
Radiat Res. 2013 Sep;180(3):292-8. doi: 10.1667/RR3240.1. Epub 2013 Aug 8.
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.
辐射增强癌细胞侵袭性的能力与炎症反应有关，几乎所有接受辐射的患者都会引发炎症反应。对于乳腺癌患者，放射治疗完成后几周内，炎症细胞因子白细胞介素-1β（IL1β）的血浆水平持续升高。本研究旨在确定 IL1β 是否参与放射诱导的乳腺癌细胞侵袭增强。通过侵袭室评估了 IL1β 的作用，其中辐照成纤维细胞被用作上层腔室中种植的 MDA-MB-231 乳腺癌细胞的趋化剂。还确定了 IL1β 刺激 MDA-MB-231 细胞中环氧化酶-2（COX-2）表达和前列腺素 E2（PGE2）生物合成的能力。我们的结果表明，用抗 IL1β 抗体可预防 MDA-MB-231 细胞侵袭的放射增强。辐照成纤维细胞中产生的 IL1β 增加，而未暴露于辐照成纤维细胞的 MDA-MB-231 细胞的侵袭性则通过添加这种细胞因子得到促进。此外，添加 COX-2 抑制剂 NS-398 可阻止辐照成纤维细胞或 IL1β 诱导的癌细胞侵袭的刺激。我们提出，IL1β 对 MDA-MB-231 细胞侵袭性的影响涉及基质金属蛋白酶-9（MMP-9）产生的升高、COX-2 表达的诱导和 PGE2 生物合成。总之，这项研究支持 IL1β 参与放射增强乳腺癌细胞侵袭。
