2018 Fiscal Year Final Research Report

Expression of annexin II and stromal tenascin C promotes epithelial to mesenchymal transition and correlates with distant metastasis in pancreatic cancer

Research Project

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Project/Area Number	16K15607
Research Category	Grant-in-Aid for Challenging Exploratory Research
Allocation Type	Multi-year Fund
Research Field	Digestive surgery
Research Institution	Chiba University
Principal Investigator	Takano Shigetsugu 千葉大学, 大学院医学研究院, 助教 (20436380)
Co-Investigator(Kenkyū-buntansha)	佐藤守千葉大学, 医学部附属病院, 特任准教授 (20401002) 吉富秀幸千葉大学, 大学院医学研究院, 准教授 (60375631) 宮崎勝国際医療福祉大学, 大学病院, 教授 (70166156) 酒井望千葉大学, 医学部附属病院, 助教 (70436385) 賀川真吾千葉大学, 医学部附属病院, 助教 (90507302)
Project Period (FY)	2016-04-01 – 2019-03-31
Keywords	膵癌
Outline of Final Research Achievements	The interaction of cancer cells and stromal components contributes to cancer progression. We explored the correlation of annexin II (ANX2) and stromal tenascin C (TNC) with pancreatic cancer (PDAC) progression. In ANX2 knockdown cells, there were fewer cells with a mesenchymal appearance in 3D culture and reduced invasion. Morphological change into mesenchymal phenotype and invasion were enhanced more by recombinant TNC treatment in control cells but not in ANX2 knockdown cells. Pancreatosphere formation assays showed that both ANX2 and TNC facilitated stem-like characters, and anoikis assays indicated that the ANX2-TNC interaction contributes to anoikis resistance in PDAC cells. In IHC analyses, the ANX2 High/stromal TNC High expression group showed a significant correlation with distant metastasis and poor outcomes after surgery. In conclusion, ANX2 and stromal TNC regulate invasion along with stemness and anoikis resistance, which are crucial for metastasis in PDAC progression.
Free Research Field	肝胆膵外科
Academic Significance and Societal Importance of the Research Achievements	膵癌は最も予後不良な癌であり、５年生存率は未だ１０％に満たない疾患である。その最大の理由の１つとして挙げられるのは、膵癌自体の悪性度の高さ（浸潤・転移能）と考えられる。本研究でAnnexin-IIとTenascin Cによる、癌細胞と癌周囲微小環境の相互作用について明らかとなったことで、膵癌進展機序の解明および今後の新規治療開発につながる研究成果と考えられる。本研究の内容については2018年 International Journal of Molecular Medicineに受理され、論文報告された。