PLOD2 as a potential regulator of peritoneal dissemination in gastric cancer

Yuki Kiyozumi, Masaaki Iwatsuki, Junji Kurashige, Yoko Ogata, Kohei Yamashita, Yuki Koga, Tasuku Toihata, Yukiharu Hiyoshi, Takatsugu Ishimoto, Yoshifumi Baba, Yuji Miyamoto, Naoya Yoshida, Kazuyoshi Yanagihara, Koshi Mimori, Hideo Baba

研究成果: ジャーナルへの寄稿学術誌査読

18 被引用数 (Scopus)

抄録

Peritoneal dissemination is the most common metastatic pattern in advanced gastric cancer (GC) and has a very poor prognosis. However, its molecular mechanism has not been elucidated. Our study investigated genes associated with peritoneal dissemination of GC. We performed combined expression analysis of metastatic GC cell lines and identified Procollagen-lysine, 2-oxoglutarate 5-dioxygenase2 (PLOD2) as a potential regulator of peritoneal dissemination. PLOD2 is regulated by hypoxia-inducible factor-1 (HIF-1) and mediates extracellular matrix remodeling, alignment, and mechanical properties. We analyzed PLOD2 expression immunohistochemically in 179 clinical samples, and found high PLOD2 expression to be significantly associated with peritoneal dissemination, leading to poor prognosis. In an in vivo-collected metastatic cell line, downregulation of PLOD2 by siRNA reduced invasiveness and migration. Hypoxia upregulated PLOD2 mediated by HIF-1, and promoted invasiveness and migration. After exposure to hypoxia, a cell line transfected with siPLOD2 exhibited significantly suppressed invasiveness and migration, despite high HIF-1 expression. These findings indicate that PLOD2 is a regulator of, and candidate therapeutic target for peritoneal dissemination of GC. Although peritoneal dissemination of GC has a very poor prognosis, its molecular mechanism has not been elucidated. We identified PLOD2 regulated by HIF-1 as a potential regulator of peritoneal dissemination of GC. Finally, we showed that PLOD2 promotes cell invasiveness and migration in GC under hypoxia and lead to peritoneal dissemination of GC.

本文言語英語
ページ(範囲)1202-1211
ページ数10
ジャーナルInternational Journal of Cancer
143
5
DOI
出版ステータス出版済み - 9月 1 2018

!!!All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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