Kim Sung Dae, Yi Joo Mi, Park Moon-Taek
Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan 46033, Republic of Korea.
Department of Microbiology and Immunology, College of Medicine, Inje University, Busan 47392, Republic of Korea.
Oncol Lett. 2019 Feb;17(2):2187-2196. doi: 10.3892/ol.2018.9833. Epub 2018 Dec 14.
The tumor microenvironment is closely associated with tumor malignancy, and includes tumor relapse and metastasis trigged by epithelial-mesenchymal transition (EMT), which leads to the expansion of cancer stem-like cells. Radiotherapy is known to acutely and persistently affect changes in this tumor microenvironment by altering the vascular functions of tumor endothelial cells. However, the precise role of endothelial cells in tumor malignancy following treatment with irradiation has not been completely elucidated. The present study investigated the differences in malignant behavior of liver cancer cells in response to irradiated endothelial cells. To achieve this, a co-cultivation system was established to identify the potential role of endothelial cells in malignant liver cancer cells using medium conditioned with endothelial cells. It was observed that the medium conditioned by endothelial cells when irradiated with a single dose (2 Gy), greatly increased the migratory and invasive properties of liver cancer cells, as well as inducing mesenchymal markers, and enhancing the sphere-forming ability of liver cancer cells, The mRNA levels of genes regulating the self-renewal of cancer stem cells were increased in liver cancer cells by treatment with medium conditioned with endothelial cells. However, neither the medium conditioned by endothelial cells irradiated with fractionated doses (2 Gy × 3; 2 Gy/day for 3 days) or with a single dose (6 Gy) greatly influenced the malignancy of liver cancer cells. In conclusion, the data obtained by the present study indicated that 2 Gy irradiation of endothelial cells influenced the increase in tumor malignancy in liver cancer cells. Furthermore, the distinct differences in the indirect effects of ionizing radiation on tumor malignancy may provide valuable information for the improvement in the efficacy of radiotherapy.
肿瘤微环境与肿瘤恶性程度密切相关，包括由上皮-间质转化（EMT）引发的肿瘤复发和转移，这会导致癌症干细胞样细胞的扩增。已知放疗通过改变肿瘤内皮细胞的血管功能，对这种肿瘤微环境产生急性和持续性影响。然而，放疗后内皮细胞在肿瘤恶性程度中的精确作用尚未完全阐明。本研究调查了肝癌细胞对受辐照内皮细胞反应的恶性行为差异。为此，建立了共培养系统，使用内皮细胞条件培养基来确定内皮细胞在恶性肝癌细胞中的潜在作用。观察到，单次剂量（2 Gy）辐照后的内皮细胞条件培养基，极大地增加了肝癌细胞的迁移和侵袭特性，诱导了间充质标志物，并增强了肝癌细胞的成球能力。用内皮细胞条件培养基处理后，肝癌细胞中调节癌症干细胞自我更新的基因的mRNA水平升高。然而，分次剂量（2 Gy×3；连续3天，每天2 Gy）或单次剂量（6 Gy）辐照后的内皮细胞条件培养基，均未对肝癌细胞的恶性程度产生显著影响。总之，本研究获得的数据表明，2 Gy辐照内皮细胞会影响肝癌细胞肿瘤恶性程度的增加。此外，电离辐射对肿瘤恶性程度的间接影响的明显差异，可能为提高放疗疗效提供有价值的信息。
