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

Abstract

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.