College of Medicine, 89481Chosun University, Gwangju, Republic of Korea.
34926Jeju National University, Jeju, Republic of Korea.
Technol Cancer Res Treat. 2021 Jan-Dec;20:15330338211038487. doi: 10.1177/15330338211038487.
: To investigate a feasible candidate for an appropriate cell line for the orthotopic renal cell carcinoma (RCC) model. Normal human proximal tubule cells (HK-2) and RCC cells were used for MTT assay, Western blotting, sphere-forming assay, and orthotopic injection of BALB/c-nude mice. Immunohistochemistry was adopted in tissue arrays and orthotopic tumors. Primary RCC cells showed resistance to a GPX4 inhibitor compared to HK-2 and to metastatic RCC cells, Caki-1. Caki-2 and SNU-333 cells showed resistance to ferroptosis via increased GPX4 and FTH1, respectively. RCC cells showed increased αSMA, in which Caki-2 and SNU-333 cells exhibited different epithelial-mesenchymal transition and cancer stem cell markers. Caki-1 and SNU-333 cells formed spheres in vitro and orthotopic tumor masses in vivo. The injected SNU-333 tumor only showed high intensities of CD10 and PAX8, markers of renal origin. SNU-333 cell line exhibited resistance via iron metabolism and stemness, and had tumor-initiating capacities in vitro and in vivo. These results suggest that among the cells tested, SNU-333 cells were the most promising for the establishment of an orthotopic RCC model for further researches.
: 为了寻找合适的肾细胞癌（RCC）模型的原代细胞系，我们对正常人类近端肾小管细胞（HK-2）和 RCC 细胞进行了 MTT 检测、western blot 检测、球体形成实验和裸鼠原位注射。我们在组织芯片和原位肿瘤中使用了免疫组织化学方法。与 HK-2 和转移性 RCC 细胞 Caki-1 相比，原代 RCC 细胞对 GPX4 抑制剂表现出耐药性。Caki-2 和 SNU-333 细胞通过增加 GPX4 和 FTH1 分别对铁死亡产生耐药性。RCC 细胞表达了更多的αSMA，其中 Caki-2 和 SNU-333 细胞表现出不同的上皮-间充质转化和癌症干细胞标志物。Caki-1 和 SNU-333 细胞在体外形成球体并在体内形成原位肿瘤。注射的 SNU-333 肿瘤仅表现出 CD10 和 PAX8 的高强度表达，这是肾脏来源的标志物。SNU-333 细胞系通过铁代谢和干细胞特性表现出耐药性，并且具有体外和体内的肿瘤起始能力。这些结果表明，在所测试的细胞中，SNU-333 细胞是建立 RCC 原位模型的最有前途的候选细胞。
