Bystander effects induced by the interaction between urothelial cancer cells and irradiated adipose tissue-derived stromal cells in urothelial carcinoma
Bystander effects induced by the interaction between urothelial cancer cells and irradiated adipose tissue-derived stromal cells in urothelial carcinoma
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DOI：
10.1007/s13577-022-00668-7
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发表时间：
2022-01-19
期刊：
影响因子：
4.3
通讯作者：
Noguchi, Mitsuru
中科院分区：
文献类型：
--
作者：
Kawasaki, Maki;Nagase, Kei;Noguchi, Mitsuru
已知癌细胞与邻近脂肪组织源性基质细胞（ATSC）之间的细胞间相互作用可以调节癌细胞的侵袭性。此外，辐射引起的旁观者效应是癌细胞动力学的重要调节剂。放射治疗通常用于治疗泌尿系癌症，但受辐射的癌症基质（包括脂肪组织）对尿路上皮癌（UC）的生物学效应仍不清楚。我们使用胶原凝胶培养方法研究了受辐射 ATSC 对 UC 的旁观者效应，以复制单次 12 Gy 剂量辐射后受辐射 ATSC 与癌细胞的相互作用。分析了 p53 结合蛋白-1 (53BP1) 的增殖活性、侵袭能力、蛋白表达和核转位。与未受辐射的对照组相比，受辐射的 ATSC 显着抑制了 UC 细胞的生长并促进了细胞凋亡。受辐射的 ATSC 增加了 UC 细胞的侵袭性，但受辐射的成纤维细胞却没有增加。在照射组中证实了由于旁观者效应导致的53BP1蛋白的核易位。受辐射的 ATSCs 调节 UC 中胰岛素受体、胰岛素样生长因子-1 和细胞外信号调节激酶-1/2 的表达。总之，受辐射 ATSC 的旁观者效应是 UC 的关键调节因子，其作用根据所涉及的间充质细胞的类型而有所不同。我们的替代文化模型是进一步研究多种癌症放射治疗的有前途的工具。
Cell-cell interactions between cancer cells and neighboring adipose tissue-derived stromal cells (ATSCs) are known to regulate the aggressiveness of cancer cells. In addition, the radiation-induced bystander effect is an important modulator of cancer cell kinetics. Radiation therapy is often given for urinary cancer, but the biological effects of the irradiated cancer stroma, including adipose tissue, on urothelial carcinoma (UC) remain unclear. We investigated the bystander effect of irradiated ATSCs on UC using a collagen gel culture method to replicate irradiated ATSC-cancer cell interactions after a single 12-Gy dose of irradiation. Proliferative activity, invasive capacity, protein expression and nuclear translocation of p53 binding protein-1 (53BP1) were analyzed. Irradiated ATSCs significantly inhibited the growth and promoted the apoptosis of UC cells in comparison to non-irradiated controls. The invasiveness of UC cells was increased by irradiated ATSCs, but not irradiated fibroblasts. Nuclear translocation of 53BP1 protein due to the bystander effect was confirmed in the irradiated group. Irradiated ATSCs regulated the expressions of the insulin receptor, insulin-like growth factor-1 and extracellular signal-regulated kinase-1/2 in UC. In conclusion, the bystander effect of irradiated ATSCs is a critical regulator of UC, and the actions differed depending on the type of mesenchymal cell involved. Our alternative culture model is a promising tool for further investigations into radiation therapy for many types of cancer.