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 Miyawaki; Hitoshi Kusaba; Koichi Akashi; Eishi Baba

doi:10.1111/cas.13777

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

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Abstract

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.

Original language	English
Pages (from-to)	3461-3470
Number of pages	10
Journal	Cancer Science
Volume	109
Issue number	11
DOIs	https://doi.org/10.1111/cas.13777
Publication status	Published - Nov 2018

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/cas.13777

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Nakano, M., Ito, M., Tanaka, R., Ariyama, H., Mitsugi, K., Makiyama, A., Uchino, K., Esaki, T., Tsuruta, N., Hanamura, F., Yamaguchi, K., Okumura, Y., Sagara, K., Takayoshi, K., Nio, K., Tsuchihashi, K., Tamura, S., Shimokawa, H., Arita, S., ... Baba, E. (2018). Epithelial-mesenchymal transition is activated in CD44-positive malignant ascites tumor cells of gastrointestinal cancer. Cancer Science, 109(11), 3461-3470. https://doi.org/10.1111/cas.13777

Nakano, M, Ito, M, Tanaka, R, Ariyama, H, Mitsugi, K, Makiyama, A, Uchino, K, Esaki, T, Tsuruta, N, Hanamura, F, Yamaguchi, K, Okumura, Y, Sagara, K, Takayoshi, K, Nio, K, Tsuchihashi, K, Tamura, S, Shimokawa, H, Arita, S, Miyawaki, K, Kusaba, H, Akashi, K & Baba, E 2018, 'Epithelial-mesenchymal transition is activated in CD44-positive malignant ascites tumor cells of gastrointestinal cancer', Cancer Science, vol. 109, no. 11, pp. 3461-3470. https://doi.org/10.1111/cas.13777

@article{d55cdd63c84f4c0390c13a88279e98cd,

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

abstract = "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.",

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

note = "Funding Information: This study was supported in part by the Japan Society for the Pro- Funding Information: This study was supported in part by the Japan Society for the Promotion of Science, and KMOG, a non-profit organization. The primary tissues of colorectal, gastric and pancreatic cancer were provided by N. Torada, T. Ueki, T. Manabe and M. Nakamura from the Department of Surgery and Oncology, Kyushu University. Co-workers from our laboratories, A. Yurino, Y. Ohmura and T. Yoshihiro, supported this work. Publisher Copyright: {\textcopyright} 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.",

year = "2018",

month = nov,

doi = "10.1111/cas.13777",

language = "English",

volume = "109",

pages = "3461--3470",

journal = "Cancer Science",

issn = "1347-9032",

publisher = "Wiley-Blackwell",

number = "11",

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TY - JOUR

T1 - Epithelial-mesenchymal transition is activated in CD44-positive malignant ascites tumor cells of gastrointestinal cancer

AU - Nakano, Michitaka

AU - Ito, Mamoru

AU - Tanaka, Risa

AU - Ariyama, Hiroshi

AU - Mitsugi, Kenji

AU - Makiyama, Akitaka

AU - Uchino, Keita

AU - Esaki, Taito

AU - Tsuruta, Nobuhiro

AU - Hanamura, Fumiyasu

AU - Yamaguchi, Kyoko

AU - Okumura, Yuta

AU - Sagara, Kosuke

AU - Takayoshi, Kotoe

AU - Nio, Kenta

AU - Tsuchihashi, Kenji

AU - Tamura, Shingo

AU - Shimokawa, Hozumi

AU - Arita, Shuji

AU - Miyawaki, Kohta

AU - Kusaba, Hitoshi

AU - Akashi, Koichi

AU - Baba, Eishi

N1 - Funding Information: This study was supported in part by the Japan Society for the Pro- Funding Information: This study was supported in part by the Japan Society for the Promotion of Science, and KMOG, a non-profit organization. The primary tissues of colorectal, gastric and pancreatic cancer were provided by N. Torada, T. Ueki, T. Manabe and M. Nakamura from the Department of Surgery and Oncology, Kyushu University. Co-workers from our laboratories, A. Yurino, Y. Ohmura and T. Yoshihiro, supported this work. Publisher Copyright: © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

PY - 2018/11

Y1 - 2018/11

N2 - 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.

AB - 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.

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U2 - 10.1111/cas.13777

DO - 10.1111/cas.13777

M3 - Article

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AN - SCOPUS:85054011127

SN - 1347-9032

VL - 109

SP - 3461

EP - 3470

JO - Cancer Science

JF - Cancer Science

IS - 11

ER -

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

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