Department of Biological and Medical Sciences, Oxford Brookes University, Oxford OX3 0BP, UK.
Int J Mol Sci. 2021 Oct 26;22(21):11570. doi: 10.3390/ijms222111570.
Along with the cells that are exposed to radiation, non-irradiated cells can unveil radiation effects as a result of intercellular communication, which are collectively defined as radiation induced bystander effects (RIBE). Exosome-mediated signalling is one of the core mechanisms responsible for multidirectional communication of tumor cells and their associated microenvironment, which may result in enhancement of malignant tumor phenotypes. Recent studies show that exosomes and exosome-mediated signalling also play a dynamic role in RIBE in cancer cell lines, many of which focused on altered exosome cargo or their effects on DNA damage. However, there is a lack of knowledge regarding how these changes in exosome cargo are reflected in other functional characteristics of cancer cells from the aspects of invasiveness and metastasis. Therefore, in the current study, we aimed to investigate exosome-mediated bystander effects of 2 Gy X-ray therapeutic dose of ionizing radiation on the invasive potential of MCF-7 breast cancer cells in vitro via assessing Matrigel invasion potential, epithelial mesenchymal transition (EMT) characteristics and the extent of glycosylation, as well as underlying plausible molecular mechanisms. The findings show that exosomes derived from irradiated MCF-7 cells enhance invasiveness of bystander MCF-7 cells, possibly through altered miRNA and protein content carried in exosomes.
与暴露于辐射的细胞一起,非辐射细胞可以由于细胞间通讯而揭示辐射效应,这些效应被统称为辐射诱导的旁观者效应(RIBE)。外泌体介导的信号转导是肿瘤细胞及其相关微环境进行多向通讯的核心机制之一,这可能导致恶性肿瘤表型的增强。最近的研究表明,外泌体和外泌体介导的信号转导在癌细胞系中的 RIBE 中也发挥着动态作用,其中许多研究集中在改变的外泌体货物或它们对 DNA 损伤的影响上。然而,对于外泌体货物的这些变化如何反映在癌症细胞的其他功能特性(侵袭性和转移性)方面,我们知之甚少。因此,在本研究中,我们旨在通过评估 Matrigel 侵袭潜力、上皮间质转化(EMT)特征和糖基化程度以及潜在的分子机制,研究 2 Gy 射线治疗剂量电离辐射对 MCF-7 乳腺癌细胞体外侵袭潜力的外泌体介导的旁观者效应。研究结果表明,来自辐照 MCF-7 细胞的外泌体增强了旁观者 MCF-7 细胞的侵袭性,这可能是通过外泌体中携带的改变的 miRNA 和蛋白质含量实现的。