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

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.

• Authors: 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
• Journal: Journal of clinical biochemistry and nutrition (J Clin Biochem Nutr) Vol. 55 Issue 1 Pg. 56-61 (Jul 2014) ISSN: 0912-0009 [Print] Japan
• PMID: 25120280 (Publication Type: Journal Article)