TITLE:
Characterization of the Stem Cell Fraction in Pancreatobiliary Carcinomas: The Notch Signaling Pathway as a Potential Therapeutic Target
AUTHORS:
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
KEYWORDS:
Notch Pathway, Cancer Stem Cells, Pancreatic Adenocarcinoma, Extrahepatic Cholangiocarcinoma, Targeted Therapy
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.9 No.6,
June
8,
2018
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.