Enhanced KRT13 gene expression bestows radiation resistance in squamous cell carcinoma cells

In Vitro Cell Dev Biol Anim. 2021 Mar;57(3):300-314. doi: 10.1007/s11626-020-00542-6. Epub 2021 Feb 3.

Abstract

Cancer metastasis and recurrence are potentially lethal. A small number of cancer cell groups called cancer stem cells (CSCs) have both stem cell capacity and cancer-forming ability and are reported to play important roles in cancer metastasis and recurrence. These CSCs are considered to be radiation-resistant (RR). Therefore, understanding the biological effects of radiation on squamous cell carcinoma (SCC) cell lines in vitro and in vivo might be worthwhile to circumvent radiation resistance. Currently, there are no reports on the establishment of RR-SCC cells in serum-free defined culture, which mimics biological mechanisms and prevents instability of using serum in the culture medium. We isolated radiation-resistant strains, designated A431-LDR and A431-HDR, from A431 cells derived from vulval SCC and irradiated them with a total dose of 60 Gy at a low-dose rate (2.2 Gy/d) (RM1000) and a high-dose rate (5 Gy/5.75min) in serum-free defined culture. These cells exhibited high sphere-forming and migration ability in vitro and high tumor-forming ability in nude mice xenografts. Overexpression of KRT13 in A431-RR cells might play a role in its radiation-resistant characteristics. These cells might be useful not only to study cancer stem cells but also to study the circumvention of radiation resistance by novel cancer treatment modalities.

Keywords: KRT13; Radiation-resistant carcinoma cell strains; Serum-free defined culture.

MeSH terms

  • Animals
  • Carcinogenesis / pathology
  • Carcinogenesis / radiation effects
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Movement / radiation effects
  • Cell Proliferation / radiation effects
  • Culture Media, Serum-Free
  • Dose-Response Relationship, Radiation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Keratin-13 / genetics*
  • Keratin-13 / metabolism
  • Mice
  • Mice, Nude
  • Neoplastic Stem Cells / pathology
  • Neoplastic Stem Cells / radiation effects
  • RNA, Small Interfering / metabolism
  • Radiation Tolerance / genetics*
  • Tumor Stem Cell Assay
  • Vulvar Neoplasms / genetics*
  • Vulvar Neoplasms / pathology

Substances

  • Culture Media, Serum-Free
  • KRT13 protein, human
  • Keratin-13
  • RNA, Small Interfering