Open AccessEpithelial‐mesenchymal transition is activated in CD 44‐positive malignant ascites tumor cells of gastrointestinal cancer
Author(s) -
Nakano Michitaka,
Ito Mamoru,
Tanaka Risa,
Ariyama Hiroshi,
Mitsugi Kenji,
Makiyama Akitaka,
Uchino Keita,
Esaki Taito,
Tsuruta Nobuhiro,
Hanamura Fumiyasu,
Yamaguchi Kyoko,
Okumura Yuta,
Sagara Kosuke,
Takayoshi Kotoe,
Nio Kenta,
Tsuchihashi Kenji,
Tamura Shingo,
Shimokawa Hozumi,
Arita Shuji,
Miyawaki Kohta,
Kusaba Hitoshi,
Akashi Koichi,
Baba Eishi
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13777
Subject(s) - ascites , smad , epithelial–mesenchymal transition , flow cytometry , immunohistochemistry , cancer , cancer research , transforming growth factor , transforming growth factor beta , biology , in vitro , pathology , chemistry , medicine , immunology , endocrinology , metastasis , biochemistry
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 CD 44 + 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 SMAD 2 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 ATC revealed high frequencies of CD 44 and possessed distinct EMT features from primary tissues that were mainly maintained by TGF ‐beta 1 in the ascites.