Deregulation of nicotinamide N-methyltransferase and gap junction protein alpha-1 causes metastasis in adenoid cystic carcinoma

Kana Ishibashi, kotaro ishii, Goro Sugiyama, Tomoki Sumida, Tsuyoshi Sugiura, Yu Kamata, Katsuhiro Seki, Takahiro Fujinaga, Kumamaru Wataru, Yosuke Kobayashi, Naomi Hiyake, Hiroyuki Nakano, Tomohiro Yamada, Yoshihide Mori

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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.

Original languageEnglish
Pages (from-to)187-197
Number of pages11
JournalAnticancer Research
Volume38
Issue number1
DOIs
Publication statusPublished - Jan 1 2018

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Nicotinamide N-Methyltransferase
Adenoid Cystic Carcinoma
Connexins
Neoplasm Metastasis
Cell Line
Epithelial-Mesenchymal Transition
Neoplastic Stem Cells
Tumor Biomarkers
Salivary Glands
Oligonucleotide Array Sequence Analysis
Carcinogenesis
Up-Regulation
Down-Regulation
Transplantation
Biomarkers
Lymph Nodes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Deregulation of nicotinamide N-methyltransferase and gap junction protein alpha-1 causes metastasis in adenoid cystic carcinoma. / Ishibashi, Kana; ishii, kotaro; Sugiyama, Goro; Sumida, Tomoki; Sugiura, Tsuyoshi; Kamata, Yu; Seki, Katsuhiro; Fujinaga, Takahiro; Wataru, Kumamaru; Kobayashi, Yosuke; Hiyake, Naomi; Nakano, Hiroyuki; Yamada, Tomohiro; Mori, Yoshihide.

In: Anticancer Research, Vol. 38, No. 1, 01.01.2018, p. 187-197.

Research output: Contribution to journalArticle

Ishibashi, Kana ; ishii, kotaro ; Sugiyama, Goro ; Sumida, Tomoki ; Sugiura, Tsuyoshi ; Kamata, Yu ; Seki, Katsuhiro ; Fujinaga, Takahiro ; Wataru, Kumamaru ; Kobayashi, Yosuke ; Hiyake, Naomi ; Nakano, Hiroyuki ; Yamada, Tomohiro ; Mori, Yoshihide. / Deregulation of nicotinamide N-methyltransferase and gap junction protein alpha-1 causes metastasis in adenoid cystic carcinoma. In: Anticancer Research. 2018 ; Vol. 38, No. 1. pp. 187-197.
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AU - Sumida, Tomoki

AU - Sugiura, Tsuyoshi

AU - Kamata, Yu

AU - Seki, Katsuhiro

AU - Fujinaga, Takahiro

AU - Wataru, Kumamaru

AU - Kobayashi, Yosuke

AU - Hiyake, Naomi

AU - Nakano, Hiroyuki

AU - Yamada, Tomohiro

AU - Mori, Yoshihide

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N2 - 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.

AB - 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.

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