Kurota Yuta, Takeda Yuji, Ichiyanagi Osamu, Saitoh Shinichi, Ito Hiromi, Naito Sei, Asao Hironobu, Tsuchiya Norihiko
Department of Urology, Faculty of Medicine, Yamagata University, 2-2-2, Iida-Nishi, Yamagata 990-9585, Japan.
Department of Immunology, Faculty of Medicine, Yamagata University, 2-2-2, Iida-Nishi, Yamagata 990-9585, Japan.
Biomedicines. 2023 Apr 30;11(5):1330. doi: 10.3390/biomedicines11051330.
The regulation of the redox balance in the tumor microenvironment is thought to be an adaptive response of tumor cells to hypoxic environments. In recent years, it has been reported that the hemoglobin β-chain (HBB), which is involved in scavenging reactive oxygen species (ROS), is expressed in several carcinomas. However, the relationship between HBB expression and the prognosis of renal cell carcinoma (RCC) remains unclear.
HBB expression was immunohistochemically analyzed in 203 nonmetastatic clear cell RCC (ccRCC) cases. Cell proliferation, invasion, and ROS production were measured in ccRCC cell lines treated with HBB-specific siRNA.
The prognosis of HBB-positive patients was worse than that of HBB-negative patients. Cell proliferation and invasion were inhibited, and ROS production was increased by treatment with HBB-specific siRNA. Oxidative stress increased HBB expression in cells exposed to HO.
HBB expression in ccRCC contributes to cancer cell proliferation by suppressing ROS production under hypoxic conditions. Taken together with clinical results and in vitro experiments, HBB expression may serve as a new prognostic biomarker for RCC in the future.
肿瘤微环境中氧化还原平衡的调节被认为是肿瘤细胞对缺氧环境的一种适应性反应。近年来,有报道称参与清除活性氧(ROS)的血红蛋白β链(HBB)在几种癌症中均有表达。然而,HBB表达与肾细胞癌(RCC)预后之间的关系仍不清楚。
对203例非转移性透明细胞肾细胞癌(ccRCC)病例进行HBB表达的免疫组织化学分析。在用HBB特异性siRNA处理的ccRCC细胞系中测量细胞增殖、侵袭和ROS产生。
HBB阳性患者的预后比HBB阴性患者差。用HBB特异性siRNA处理可抑制细胞增殖和侵袭,并增加ROS产生。氧化应激增加了暴露于HO的细胞中HBB的表达。
ccRCC中HBB的表达通过在缺氧条件下抑制ROS产生来促进癌细胞增殖。结合临床结果和体外实验,HBB表达未来可能作为RCC的一种新的预后生物标志物。