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

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...

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Published in:Journal of Clinical Biochemistry and Nutrition 2014, Vol.55(1), pp.56-61
Main Authors: Kimura-Tsuchiya, Reiko, Ishikawa, Takeshi, Kokura, Satoshi, Mizushima, Katsura, Adachi, Satoko, Okajima, Manabu, Matsuyama, Tatsuzo, Okayama, Tetsuya, Sakamoto, Naoyuki, Katada, Kazuhiro, Kamada, Kazuhiro, Uchiyama, Kazuhiko, Handa, Osamu, Takagi, Tomohisa, Yagi, Nobuaki, Naito, Yuji, Itoh, Yoshito
Format: Article
Language:English
Subjects:
epithelial-mesenchymal transition
heat treatment
hyperthermia
Original
pancreatic cancer
TGF-β1
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Summary: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.
ISSN:0912-0009
1880-5086
DOI:10.3164/jcbn.14-8