| セッション情報 | The 4th International ForumII Challenge to the pancreatic and biliary cancers 1. Pancreatic and biliary cancers―Challenge to the pathogenesis |
|---|---|
| タイトル | IFII-1-4：Involvement of epithelial to mesenchymal transition and its related molecules in the development of pancreatic ductal adenocarcinoma |
| 演者 | Satoh Kennichi（Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, Japan） |
| 共同演者 | Hamada Shin（Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan）, Shimosegawa Tooru（Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan） |
| 抄録 | Epithelial to mesenchymal transition（EMT）plays a pivotal role in cancer cell invasion and metastasis. In addition, recent studies show the association of EMT with chemoresistance and property of cancer stem cell（CSC）, indicating that EMT is a key factor for the development of PDAC. Therefore, we have investigated the acquisition of aggressive traits linked to EMT and the regulatory mechanism to clarify the pathogenesis of PDAC development. We first assessed how EMT facilitates PDAC development. We previously showed that MSX2 was an inducer of EMT in PDAC enhancing metastatic ability. Thus, we examined whether MSX2 would be involved in chemoresistance and CSC phenotype. As expected, MSX2 expressing PDAC cells demonstrated the resistance to gemcitabine. Furthermore, forced or reduced expression of MSX2 in PDAC gave rise to increased or decreased numbers of side population（SP）cells, which have been shown to contain putative CSC fraction, respectively. We next conducted comprehensive analysis of microRNA（miRNA）expression profiles in PDAC and non-invasive intraductal papillary mucinous neoplasms（IPMNs）to explore the regulator of EMT in PDAC. From this analysis, we identified miR126 as a down-regulated miR, and miR197 and miR365 as up-regulated miRs, specifically in PDAC. Re-expression of miR126 by miR precursor transfection attenuated PDAC cell migration and invasion, and induced E-cadherin expression. Forced expression of miR197 in PDAC cells enhanced cellular migration and invasion via induction of EMT. In addition, PDAC cells expressing miR365 showed gemcitabine resistance. These findings indicate that EMT inducer, MSX2, facilitates the development of PDAC through enhancement aggressive phenotype associated with EMT. In addition, miRs might also contribute to this process through regulation of EMT. |
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