Characterization of the Stem Cell Fraction in Pancreatobiliary Carcinomas: The Notch Signaling Pathway as a Potential Therapeutic Target

作     者：Elisabeth Seidel Cynthia de Carvalho Fischer Christopher Neumann Anja Reutzel-Selke Andreas Andreou Joseph Gassner Julia Gogolok Peter Tang Anja Schirmeier Fritz Klein Igor M. Sauer Johann Pratschke Marcus Bahra Rosa B. Schmuck 

作者机构：Charité—Universitatsmedizin Berlin Corporate Member of Freie Universitat Berlin Humboldt-Universitatzu Berlin and Berlin Institute of Health Institute of Surgery Augustenburger Platz 1 Berlin Germany 

出 版 物：《Journal of Cancer Therapy》 (癌症治疗（英文）)

年 卷 期：2018年第9卷第6期

页      面：480-502页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：Notch Pathway Cancer Stem Cells Pancreatic Adenocarcinoma Extrahepatic Cholangiocarcinoma Targeted Therapy 

摘      要：Pancreatic adenocarcinoma (PDAC) and extrahepatic cholangiocarcinoma (ECC) are highly lethal malignancies with limited treatment options. Both a small subpopulation of cancer stem cells (CSC) and the deregulation of the notch pathway have been considered potential sources of tumor formation. In this study, flow cytometry (FCM) was conducted to identify the CSC population and Notch-associated proteins in ECC and PDAC cell lines. Additionally, the treatment effect of Gemcitabine and the specific notch-inhibitor DAPT on ECC and PDAC cell lines was evaluated. Our results show that the amount of SP cells in ECC cell lines is significantly higher than in PDAC cell lines, and that SP-ECC cells show a higher sensitivity to therapy. In conclusion, inhibition of Notch signaling with DAPT may be of therapeutic value in ECC, but seems to show no effect on more aggressive PDAC. As it could be essential for the improvement in outcomes of the ECC patients, other trials are needed to determine the role of further Notch components.