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

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. We established three AdCC cell lines by orthotropic transplantation and in vivo selection: parental, highly me...

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Published inAnticancer research Vol. 38; no. 1; pp. 187 - 197
Main Authors Ishibashi, Kana, Ishii, Kotaro, Sugiyama, Goro, Sumida, Tomoki, Sugiura, Tsuyoshi, Kamata, Y U, Seki, Katsuhiro, Fujinaga, Takahiro, Kumamaru, Wataru, Kobayashi, Yosuke, Hiyake, Naomi, Nakano, Hiroyuki, Yamada, Tomohiro, Mori, Yoshihide
Format Journal Article
LanguageEnglish
Published Greece International Institute of Anticancer Research 01.01.2018
Subjects
Adenoid
Biomarkers
Biotechnology
Deoxyribonucleic acid
Deregulation
DNA
DNA chips
DNA microarrays
Gene expression
Identification methods
Lymph nodes
Mesenchyme
Metastases
Metastasis
Methyltransferase
N-Methyltransferase
Nicotinamide
Nicotinamide N-methyltransferase
Proteins
Salivary gland
Salivary glands
Stem cells
Transplantation
Tumorigenesis
Tumors
epithelial–mesenchymal transition
metastatic cell lines
primary tumor cell lines
Adenoid cystic carcinoma
nicotinamide N-methyltransferase
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Summary: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. 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. 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. NNMT is a potential biomarker of AdCC.
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ISSN:0250-7005
1791-7530
DOI:10.21873/anticanres.12207