Faculty of Health Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Division of Radiology and Nuclear Medicine, Sapporo Medical University Hospital, Sapporo 060-8556, Japan.
Curr Issues Mol Biol. 2021 Sep 22;43(3):1203-1211. doi: 10.3390/cimb43030085.
Non-small cell lung cancer (NSCLC) is an aggressive lung cancer accounting for approximately 85% of all lung cancer patients. For the patients with Stages IIIA, IIIB, and IIIC, the 5-year survival is low though with the combination with radiotherapy and chemotherapy. In addition, the occurrence of tumor cells (repopulated tumors) that survive irradiation remains a challenge. In our previous report, we subcloned the radiation-surviving tumor cells (IR cells) using the human NSCLC cell line, H1299, and found that the expression of neuropilin-1 (-1) was upregulated in IR cells by the microarray analysis. Here, we investigated the contribution of neuropilin-1 to changes in the characteristics of IR cells. Although there were no differences in angiogenic activity in the tube formation assay between parental and IR cells, the cell motility was increased in IR cells compared to parental cells in the cell migration assay. This enhanced cell motility was suppressed by pretreatment with anti-NRP-1 antibody. Although further studies are necessary to identify other molecules associated with NRP-1, the increase in cellular motility in IR cells might be due to the contribution of NRP-1. Inhibition of NRP-1 would help control tumor malignancy in radiation-surviving NSCLC.
非小细胞肺癌（NSCLC）是一种侵袭性肺癌，约占所有肺癌患者的 85%。对于 IIIA、IIIB 和 IIIC 期的患者，尽管结合了放疗和化疗，5 年生存率仍然较低。此外，放疗后存活的肿瘤细胞（再增殖肿瘤）的发生仍然是一个挑战。在我们之前的报告中，我们使用人非小细胞肺癌细胞系 H1299 克隆了辐射存活的肿瘤细胞（IR 细胞），并通过微阵列分析发现，IR 细胞中神经纤毛蛋白-1（NRP-1）的表达上调。在这里，我们研究了 NRP-1 对 IR 细胞特征变化的贡献。尽管在管形成试验中亲本细胞和 IR 细胞之间的血管生成活性没有差异，但在细胞迁移试验中，IR 细胞的细胞迁移能力比亲本细胞增加。用抗 NRP-1 抗体预处理可抑制这种增强的细胞迁移能力。虽然还需要进一步研究来鉴定与 NRP-1 相关的其他分子，但 IR 细胞中细胞迁移能力的增加可能是由于 NRP-1 的贡献。抑制 NRP-1 将有助于控制辐射存活的 NSCLC 的肿瘤恶性程度。
