Contribution of Neuropilin-1 in Radiation-Survived Subclones of NSCLC Cell Line H1299

Curr Issues Mol Biol. 2021 Sep 22;43(3):1203-1211. doi: 10.3390/cimb43030085.

Abstract

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.

Keywords: motility; neuropilin; non-small cell lung cancer; radiotherapy; repopulated tumor.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / radiotherapy
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Movement / radiation effects
  • Gene Expression
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Integrin alphaVbeta3 / metabolism
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / radiotherapy
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Neuropilin-1 / genetics*
  • Neuropilin-1 / metabolism
  • Protein Binding
  • RNA, Messenger / genetics
  • Radiation Tolerance / genetics*
  • Vascular Endothelial Growth Factor A / biosynthesis

Substances

  • Integrin alphaVbeta3
  • RNA, Messenger
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Neuropilin-1