Establishment and characterization of a novel HPV-negative laryngeal squamous cell carcinoma cell line, FD-LSC-1, with missense and nonsense mutations of TP53 in the DNA-binding domain

Cancer Lett. 2014 Jan 1;342(1):92-103. doi: 10.1016/j.canlet.2013.08.041. Epub 2013 Aug 31.

Abstract

Laryngeal squamous cell carcinoma (LSCC) is a common malignancy in China; however, publically available LSCC cell lines are few and not established from Chinese populations. Hence, novel and well-characterized LSCC cell lines of Chinese origin are urgently needed to provide researchers with a comprehensive database for LSCC research. From 40 cases of LSCC, we established a novel cell line that was maintained for more than 100 passages in vitro and was found to have typical epithelial morphology and ultrastructure. In-depth characterization analysis revealed polyploidy in DNA content; a doubling time of some 24h; high tumorigenicity in immunodeficient mice; higher invasive potential and more sensitive to radiation and cisplatin compared with HeLa cell line; upregulated Ki67, Notch1, EGFR, and CK5 protein levels; negative infection of human papillomavirus (HPV) and mycoplasma; expression of head and neck squamous cell carcinoma (HNSCC) biomarkers; mutations of TP53 in exons 5 and 8; a near-triploid karyotype with complex structural aberrations; and dozens of dysregulated genes and miRNAs. Cell authentication testing by the American Type Culture Collection (ATCC) confirmed the human origin of this cell line. Our findings indicate that a novel and well-differentiated LSCC cell line recapitulating the primary tumor's malignant characteristics is established and well characterized. It does not match any cell lines within the ATCC database and helps to elucidate the molecular pathogenesis of LSCC.

Keywords: Carcinoma; Cell line; Characterization; Establishment; Laryngeal neoplasms; Squamous cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alphapapillomavirus / genetics
  • Animals
  • Antineoplastic Agents / pharmacology
  • Base Sequence
  • Binding Sites
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology*
  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / physiology*
  • Cell Line, Tumor / radiation effects
  • Cell Proliferation
  • Cell Shape
  • Cisplatin / pharmacology
  • Codon, Nonsense
  • DNA Mutational Analysis
  • Epiglottis / pathology
  • Gene Expression Regulation, Neoplastic
  • Genotype
  • Humans
  • Karyotype
  • Laryngeal Neoplasms / genetics
  • Laryngeal Neoplasms / pathology*
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Mutation, Missense
  • Neoplasm Transplantation
  • Protein Structure, Tertiary
  • Radiation Tolerance
  • Tumor Suppressor Protein p53 / chemistry
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • Antineoplastic Agents
  • Codon, Nonsense
  • MicroRNAs
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Cisplatin