The inhibitory effect of heat treatment against epithelial-mesenchymal transition (EMT) in human pancreatic adenocarcinoma cell lines

Reiko Kimura-Tsuchiya; Takeshi Ishikawa; Satoshi Kokura; Katsura Mizushima; Satoko Adachi; Manabu Okajima; Tatsuzo Matsuyama; Tetsuya Okayama; Naoyuki Sakamoto; Kazuhiro Katada; Kazuhiro Kamada; Kazuhiko Uchiyama; Osamu Handa; Tomohisa Takagi; Nobuaki Yagi; Yuji Naito; Yoshito Itoh

doi:10.3164/jcbn.14-8

Original Articles

The inhibitory effect of heat treatment against epithelial-mesenchymal transition (EMT) in human pancreatic adenocarcinoma cell lines

Reiko Kimura-Tsuchiya, Takeshi Ishikawa, Satoshi Kokura, Katsura Mizushima, Satoko Adachi, Manabu Okajima, Tatsuzo Matsuyama, Tetsuya Okayama, Naoyuki Sakamoto, Kazuhiro Katada, Kazuhiro Kamada, Kazuhiko Uchiyama, Osamu Handa, Tomohisa Takagi, Nobuaki Yagi, Yuji Naito, Yoshito Itoh

Author information

Reiko Kimura-Tsuchiya
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Takeshi Ishikawa
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Department of Cancer Immune Cell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Satoshi Kokura
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Kyoto Gakuen University
Katsura Mizushima
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Satoko Adachi
Department of Cancer Immune Cell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Manabu Okajima
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Tatsuzo Matsuyama
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Tetsuya Okayama
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Department of Cancer Immune Cell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Naoyuki Sakamoto
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Kazuhiro Katada
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Kazuhiro Kamada
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Kazuhiko Uchiyama
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Osamu Handa
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Tomohisa Takagi
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Nobuaki Yagi
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Yuji Naito
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Yoshito Itoh
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine

Keywords: pancreatic cancer, epithelial-mesenchymal transition, heat treatment, hyperthermia, TGF-β1

JOURNAL FREE ACCESS

2014 Volume 55 Issue 1 Pages 56-61

DOI https://doi.org/10.3164/jcbn.14-8

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Abstract

Epithelial-mesenchymal transition (EMT) plays a crucial role in cancer metastasis. In this study, we evaluated the effect of heat treatment on tumor growth factor-β1 (TGF-β1)-induced EMT in pancreatic cancer cells and tried to ascertain the mechanism related to any observed effects. Human pancreatic cancer cell lines (BxPC-3, PANC-1 and MIAPaCa-2) were stimulated by TGF-β1, and evaluated for morphological changes using immunofluorescence and EMT-related factors (i.e., E-cadherin, Vimentin, Snail or ZEB-1) using RT-PCR. To examine the effect of heat on EMT, the cancer cells were heat-treated at 43°C for 1 h then stimulated with TGF-β1. We then evaluated whether or not heat treatment changed the expression of EMT-related factors and cell migration and also whether Smad activation was inhibited in TGF-β signaling. After being treated with TGF-β1, pancreatic cancer cells resulted in EMT and cell migration was enhanced. Heat treatment inhibited TGF-β1-induced changes in morphology, inhibited the expression of EMT-related factors, and attenuated TGF-β1-induced migration in pancreatic cancer cells. Additionally, we observed that heat treatment blocked TGF-β1-induced phosphorylation of Smad2 in PANC-1 cells. Our results suggest that heat treatment can suppress TGF-β1-induced EMT and opens the possibility of a new therapeutic use of hyperthermia as a potential treatment for cancer metastasis.

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