Deregulation of Nicotinamide N-Methyltransferase and Gap Junction Protein Alpha-1 Causes Metastasis in Adenoid Cystic Carcinoma

Anticancer Res. 2018 Jan;38(1):187-197. doi: 10.21873/anticanres.12207.

Abstract

Background/aim: Adenoid cystic carcinoma (AdCC) is a malignant tumor that occurs in the salivary glands and frequently metastasizes. The aim of this study was to identify factors mediating AdCC metastasis.

Materials and methods: We established three AdCC cell lines by orthotropic transplantation and in vivo selection: parental, highly metastatic (ACCS-M-GFP), and lymph node metastatic (ACCS-LN-GFP) cells.

Results: We examined the three cell lines. DNA microarray indicated significantly altered processes in ACCS-LN-GFP cells: particularly, the expression of nicotinamide N-methyltransferase (NNMT) was enhanced the most. NNMT is associated with tumorigenesis and is a potential tumor biomarker. Concomitantly, we found-significant down-regulation of gap junction protein alpha-1. We suggest that ACCS-LN-GFP cells acquire cancer stem cell features involving the up-regulation of NNMT and the loss of gap junction protein alpha-1, leading to epithelial-mesenchymal transition and consequent AdCC metastasis.

Conclusion: NNMT is a potential biomarker of AdCC.

Keywords: Adenoid cystic carcinoma; epithelial–mesenchymal transition; metastatic cell lines; nicotinamide N-methyltransferase; primary tumor cell lines.

MeSH terms

  • Animals
  • Carcinoma, Adenoid Cystic / metabolism
  • Carcinoma, Adenoid Cystic / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Connexin 43 / metabolism*
  • Female
  • Humans
  • Mice, Nude
  • Nicotinamide N-Methyltransferase / metabolism*
  • Salivary Gland Neoplasms / metabolism
  • Salivary Gland Neoplasms / pathology*

Substances

  • Connexin 43
  • GJA1 protein, mouse
  • Nicotinamide N-Methyltransferase