論文

査読有り 筆頭著者 国際誌
2018年5月

Established gastric cancer cell lines transplantable into C57BL/6 mice show fibroblast growth factor receptor 4 promotion of tumor growth.

Cancer science
  • Masami Yamamoto
  • Sachiyo Nomura
  • Akihiro Hosoi
  • Koji Nagaoka
  • Tamaki Iino
  • Tomohiko Yasuda
  • Tomoko Saito
  • Hirokazu Matsushita
  • Eiji Uchida
  • Yasuyuki Seto
  • James R Goldenring
  • Kazuhiko Kakimi
  • Masae Tatematsu
  • Tetsuya Tsukamoto
  • 全て表示

109
5
開始ページ
1480
終了ページ
1492
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1111/cas.13569

Previously no mouse gastric cancer cell lines have been available for transplantation into C57BL/6 mice. However, a gastric cancer model in immunocompetent mice would be useful for analyzing putative therapies. N-Methyl-N-nitrosourea (MNU) was given in drinking water to C57BL/6 mice and p53 heterozygous knockout mice. Only 1 tumor from a p53 knockout mouse could be cultured and the cells s.c. transplanted into a C57BL/6 mouse. We cultured this s.c. tumor, and subcloned it. mRNA expression in the most aggressive YTN16 subline was compared to the less aggressive YTN2 subline by microarray analysis, and fibroblast growth factor receptor 4 (FGFR4) in YTN16 cells was knocked out with a CRISPR/Cas9 system and inhibited by an FGFR4 selective inhibitor, BLU9931. These transplanted cell lines formed s.c. tumors in C57BL/6 mice. Four cell lines (YTN2, YTN3, YTN5, YTN16) were subcloned and established. Their in vitro growth rates were similar. However, s.c. tumor establishment rates, metastatic rates, and peritoneal dissemination rates of YTN2 and YTN3 were lower than for YTN5 and YTN16. YTN16 established 8/8 s.c. tumors, 7/8 with lung metastases, 3/8 with lymph node metastases and 5/5 with peritoneal dissemination. FGFR4 expression by YTN16 was 121-fold higher than YTN2. FGFR4-deleted YTN16 cells failed to form s.c. tumors and showed lower rates of peritoneal dissemination. BLU9931 significantly inhibited the growth of peritoneal dissemination of YTN16. These studies present the first transplantable mouse gastric cancer lines. Our results further indicate that FGFR4 is an important growth signal receptor in gastric cancer cells with high FGFR4 expression.

リンク情報
DOI
https://doi.org/10.1111/cas.13569
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29532565
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980194
ID情報
  • DOI : 10.1111/cas.13569
  • ISSN : 1347-9032
  • PubMed ID : 29532565
  • PubMed Central 記事ID : PMC5980194

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