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 (NRP-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.

Radiotherapy is an effective approach for the treatment of various types of cancer. However, it has been reported that the malignant capacity of tumor cells is elevated in tumors that survive radiotherapy. In a previous report, we prepared radiation‐surviving tumor cells (IR cells) using the human non‐small cell lung cancer cell line H1299. In preliminary experiments, we found that expression of neuropilin 1 was up‐regulated in IR cells. Here, we investigated the contribution of neuropilin 1 to changes in cell characteristics in these radiation‐surviving cells. Expression levels of neuropilin 1 mRNA were about 1.4‐fold up‐regulated in IR cells, as compared with parental cells. Cell motility was further increased in IR cells than parental cells on cell migration assay, although there were no differences in angiogenic activity on tube formation assay. Furthermore, up‐regulation of cell motility in IR cells was suppressed by pre‐treatment with anti‐neuropilin 1 antibody. Neuropilin 1 was observed at the endosome‐like vesicles in IR cells, on which early endosome autoantigen 1(EEA1), a marker for endosome, was not co‐localized on immunofluorescence. Although further studies are necessary in order to identify other molecules associated with neuropilin 1, neuropilin 1 may be important in controlling the up‐regulation of cell motility in radiation‐surviving tumor cells.