Establishing of mouse oral carcinoma cell lines derived from transgenic mice and their use as syngeneic tumorigenesis models

BMC Cancer. 2019 Mar 29;19(1):281. doi: 10.1186/s12885-019-5486-7.

Abstract

Background: The survival of OSCC patient needs to be further improved. miR-211 is oncogenic in OSCC and its upregulation is associated with tumor progression and poor patient survival. K14-EGFP-miR-211 transgenic mice also exhibit augmented potential for OSCC induction.

Methods: Four murine OSCC cell lines, designated MOC-L1 to MOC-L4, are established from tongue tumors induced by 4-nitroquinoline 1-oxide using the K14-EGFP-miR-211 transgenic mouse model. The genetic disruption, in vitro oncogenicity, and the eligibilities of tumorigenesis and metastasis of the cell lines are analyzed.

Results: All cell lines show green fluorescence and express a range of epithelial markers. The MOC-L1, MOC-L2 and MOC-L3 cells carry missense mutations in the DNA binding domain of the p53 gene. MOC-L1 exhibits a high level of epithelial-mesenchymal transition and has the aggressive characteristics associated with this. MOC-L1 and MOC-L2 are clonogenic in vitro as well as being tumorigenic when implanted into the dermis or tongue of syngeneic recipients. Nonetheless, only MOC-L1 exhibits immense potential for local regional and distal metastasis. Since the expression of miR-196b in MOC-L1 xenografts is drastically decreased on cisplatin treatment, it would seem that targeting of miR-196b might facilitate tumor abrogation.

Conclusions: As cell lines established in this study originated from the C57BL/6 mouse, the strain most suitable for transgenic engineering, exploring the interplay of these OSCC cells with other genetically modified cells in immune-competent mice would provide important insights into OSCC pathogenesis.

Keywords: Mouse; Oral carcinoma; Tongue; miR-211; microRNA.

MeSH terms

  • 4-Nitroquinoline-1-oxide / toxicity*
  • Animals
  • Carcinoma, Squamous Cell / chemically induced
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology*
  • Cell Culture Techniques / methods*
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition
  • ErbB Receptors / genetics*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • MicroRNAs / genetics*
  • Mutation, Missense
  • Tongue Neoplasms / chemically induced
  • Tongue Neoplasms / genetics
  • Tongue Neoplasms / pathology*
  • Tumor Microenvironment
  • Tumor Suppressor Protein p53 / genetics

Substances

  • MicroRNAs
  • Mirn211 microRNA, mouse
  • Trp53 protein, mouse
  • Tumor Suppressor Protein p53
  • 4-Nitroquinoline-1-oxide
  • EGFR protein, mouse
  • ErbB Receptors