Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul, 139-706, South Korea.
Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, South Korea.
Biochem Biophys Res Commun. 2022 Dec 25;636(Pt 2):24-30. doi: 10.1016/j.bbrc.2022.10.092. Epub 2022 Oct 31.
Although radiotherapy (RT) increases the extra centrosomes of cancer cells compared to normal cells, centrosome clustering of cancer cells with amplified centrosomes ensures bipolar mitosis for cell proliferation in response to RT. Recent evidence suggests that centrosome clustering is a tumor-selective target for improving RT in breast cancer cells. However, whether centrosome de-clustering is involved in the activation of innate immunity in response to RT remains unknown. In this study, we showed that centrosome de-clustering of irradiated cancer cells modulates cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)-mediated innate immunity in monocytes and macrophages after co-culture. Centrosome de-clustering intensifies mitotic abnormalities and cytosolic dsDNA in breast cancer cells in response to irradiation. Unexpectedly, centrosome de-clustering did not modulate the cGAS-STING signaling pathway in irradiated breast cancer cells. Importantly, centrosome de-clustering activated the cGAS-STING signaling pathway in human monocytes and mouse macrophages after co-culture with irradiated breast cancer cells. Thus, our data provide the first evidence that centrosome de-clustering of irradiated breast cancer cells induces innate immunity in tumor-associated immune cells.
尽管放射治疗（RT）会使癌细胞比正常细胞增加额外的中心体，但具有扩增中心体的癌细胞的中心体聚集可确保细胞增殖的有丝分裂为两极，以响应 RT。最近的证据表明，中心体聚集是提高乳腺癌细胞 RT 效果的肿瘤选择性靶标。然而，中心体去聚集是否参与 RT 引发的固有免疫激活仍不清楚。在这项研究中，我们表明，辐照癌细胞的中心体去聚集在共培养后调节单核细胞和巨噬细胞中环鸟苷酸-腺苷酸合酶（cGAS）-干扰素基因刺激物（STING）介导的固有免疫。中心体去聚集加剧了辐照乳腺癌细胞中细胞有丝分裂异常和细胞质双链 DNA。出乎意料的是，中心体去聚集并没有调节辐照乳腺癌细胞中的 cGAS-STING 信号通路。重要的是，中心体去聚集在与辐照乳腺癌细胞共培养后激活了人单核细胞和小鼠巨噬细胞中的 cGAS-STING 信号通路。因此，我们的数据首次提供了辐照乳腺癌细胞的中心体去聚集诱导肿瘤相关免疫细胞固有免疫的证据。
