Department of Environmental Health, National Institute of Public Health, Saitama, Japan.
Adv Exp Med Biol. 2021;1329:239-251. doi: 10.1007/978-3-030-73119-9_13.
In tumor tissues, activated stromal fibroblasts, termed cancer-associated fibroblasts (CAFs), exhibit similar characteristics to myofibroblasts. CAFs promote cancer cell differentiation and invasion by releasing various factors, such as growth factors, chemokines, and matrix-degrading proteases, into neighboring tumor cells. However, the roles of tumor microenvironment in case of radiation-induced carcinogenesis remain poorly understood. We recently revealed that mitochondrial oxidative stress causes tumor microenvironment formation associated with radiation-induced cancer. Repeated low-dose fractionated radiation progressively damages fibroblast mitochondria and elevates mitochondrial reactive oxygen species (ROS) levels. Excessive mitochondrial ROS activate transforming growth factor-beta (TGF-β) signaling, thereby inducing fibroblasts activation and facilitating tumor microenvironment formation. Consequently, radiation affects malignant cancer cells directly and indirectly via molecular alterations in stromal fibroblasts, such as the activation of TGF-β and angiogenic signaling. This review summarizes for the first time the roles of mitochondrial oxidative stress in microenvironment formation associated with radiation-induced cancer. This review may help us understand the risks of exposure to low-dose radiation. The cross talk between cancer cells and stromal fibroblasts contributes to the development and progression of radiation-induced cancer.
在肿瘤组织中，被称为癌相关成纤维细胞 (CAF) 的活化基质成纤维细胞表现出与肌成纤维细胞相似的特征。CAF 通过向邻近的肿瘤细胞释放各种因子，如生长因子、趋化因子和基质降解蛋白酶，促进癌细胞分化和侵袭。然而，肿瘤微环境在辐射诱导致癌中的作用仍知之甚少。我们最近揭示，线粒体氧化应激导致与辐射诱导癌症相关的肿瘤微环境形成。重复低剂量分割辐射逐渐损害成纤维细胞的线粒体并增加线粒体活性氧 (ROS) 水平。过量的线粒体 ROS 激活转化生长因子-β (TGF-β) 信号通路，从而诱导成纤维细胞激活并促进肿瘤微环境形成。因此，辐射通过对间质成纤维细胞的分子改变，直接和间接地影响恶性癌细胞，如 TGF-β 和血管生成信号的激活。这篇综述首次总结了线粒体氧化应激在与辐射诱导癌症相关的微环境形成中的作用。这篇综述可能有助于我们了解低剂量辐射暴露的风险。癌细胞和基质成纤维细胞之间的串扰有助于辐射诱导癌症的发展和进展。
