Establishment of Mucoepidermoid Carcinoma Cell Lines from Surgical and Recurrence Biopsy Specimens

Int J Mol Sci. 2023 Jan 15;24(2):1722. doi: 10.3390/ijms24021722.

Abstract

Patients with advanced/recurrent mucoepidermoid carcinoma (MEC) have a poor prognosis. This study aimed to establish and characterize human mucoepidermoid carcinoma cell lines from the initial surgical specimen and biopsy specimen upon recurrence from the same patient to provide a resource for MEC research. MEC specimens from the initial surgical procedure and biopsy upon recurrence were used to establish cell lines. The established cell lines were cytogenetically characterized using multi-color fluorescence in situ hybridization and detection, and the sequence of the CRTC1-MAML2 chimeric gene was determined. Furthermore, the susceptibility of head and neck mucoepidermoid carcinoma to standard treatment drugs such as cisplatin, 5-fluorouracil, and cetuximab was investigated. We successfully established unique MEC cell lines, AMU-MEC1, from an initial surgical specimen and AMU-MEC1-R1 and AMU-MEC1-R2 from the recurrent biopsy specimen in the same patient. These cell lines exhibited epithelial morphology and developed in vitro-like cobblestones. They shared eight chromosomal abnormalities, including der(19)ins(19;11)(p13;?), which resulted in a chimeric CRTC1-MAML2 gene, indicating the same origin of the cell lines. The susceptibility of all cell lines to cisplatin and 5-fluorouracil was low. Interestingly, EGFR dependency for cell growth decreased in AMU-MEC-R1 and AMU-MEC-R2 but was retained in AMU-MEC1. These cytogenetic and biochemical findings suggest that the established cell lines can be used to investigate the disease progression mechanisms and develop novel therapeutics for MEC.

Keywords: 5-fluorouracil; EGFR; Multi-color FISH; cetuximab; chimeric gene; cisplatin; head and neck mucoepidermoid carcinoma; karyotype.

MeSH terms

  • Biopsy
  • Carcinoma, Mucoepidermoid* / pathology
  • Cell Line, Tumor
  • Cisplatin
  • DNA-Binding Proteins / genetics
  • Fluorouracil / pharmacology
  • Humans
  • In Situ Hybridization, Fluorescence
  • Oncogene Proteins, Fusion / genetics
  • Salivary Gland Neoplasms* / pathology
  • Trans-Activators / genetics
  • Transcription Factors / genetics

Substances

  • DNA-Binding Proteins
  • Trans-Activators
  • Cisplatin
  • Transcription Factors
  • Fluorouracil
  • Oncogene Proteins, Fusion