Epithelial-mesenchymal transition is activated in CD44-positive malignant ascites tumor cells of gastrointestinal cancer

Michitaka Nakano, Mamoru Ito, Risa Tanaka, Hiroshi Ariyama, Kenji Mitsugi, Akitaka Makiyama, Keita Uchino, Taito Esaki, Nobuhiro Tsuruta, Fumiyasu Hanamura, Kyoko Yamaguchi, Yuta Okumura, Kosuke Sagara, Kotoe Takayoshi, Kenta Nio, Kenji Tsuchihashi, Shingo Tamura, Hozumi Shimokawa, Shuji Arita, Kohta MiyawakiHitoshi Kusaba, Koichi Akashi, Eishi Baba

研究成果: Contribution to journalArticle査読

1 被引用数 (Scopus)

抄録

Disseminated cancer cells in malignant ascites possess unique properties that differ from primary tumors. However, the biological features of ascites tumor cells (ATC) have not been fully investigated. By analyzing ascites fluid from 65 gastrointestinal cancer patients, the distinguishing characteristics of ATC were identified. High frequency of CD44+ cells was observed in ATC using flow cytometry (n = 48). Multiplex quantitative PCR (n = 15) showed higher gene expression of epithelial-mesenchymal transition (EMT)-related genes and transforming growth factor beta (TGF-beta)-related genes in ATC than in the primary tissues. Immunohistochemistry (n = 10) showed that ATC also had much higher expression of phosphorylated SMAD2 than that in the corresponding primary tissues. TGF-beta 1 was detected in all cases of malignant ascites by enzyme-linked immunoassay (n = 38), suggesting the possible interaction of ATC and the ascites microenvironment. In vitro experiments revealed that these ATC properties were maintained by TGF-beta 1 in cultured ATC(n = 3). Here, we showed that ATCrevealed high frequencies of CD44 and possessed distinct EMT features from primary tissues that were mainly maintained by TGF-beta 1 in the ascites.

本文言語英語
ページ(範囲)3461-3470
ページ数10
ジャーナルCancer Science
109
11
DOI
出版ステータス出版済み - 11 2018

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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