Controversial truth: Human pancreatic cancer cell line homes cancer stem cells

Abstract

Event Abstract Back to Event Controversial truth: human pancreatic cancer cell line homes cancer stem cells Yuan Han Teh1, Rajesh Ramasamy2 and Johnson Stanslas1* 1 Department of Medicine, Faculty of Medicine and Health Sciences, University Putra Malaysia, Malaysia 2 Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Malaysia Background Pancreatic cancer stem cells (pCSCs) are the culprit of pancreatic cancer recurrence. Disputable presence of pCSCs in continuous cell line has led to an extensive application of patient-derived pCSC culture for in vitro evaluation of anti-pCSC agents. Nevertheless, the procurement of patients’ tumour biopsies can be challenging to some researchers. Here, we investigated the presence of CSCs in pancreatic cancer cell lines (PANC-1, MIA PaCa-2, Capan-2, and BxPC-3). Methods Dose-response effect of gemcitabine and vismodegib on pancreatic cancer cell lines was evaluated by MTT cell viability assay. Immunophenotyping was achieved via flow cytometry. Limiting dilution spheroid formation assay and Extreme Limiting Dilution Analysis (ELDA) software determined in vitro tumourigenicity of Capan-2 cells. Tumourspheres were treated with gemcitabine and vismodegib, followed by counting intact tumourspheres. Results Capan-2 was the most resistant cell line to gemcitabine (IC50 > 100 µM). This profound chemoresistance coincided with the presence of a cell subpopulation (3.8%) that co-expressed pCSC surface markers (CD44, CD24, and CD133), which was undetectable in other cell lines. ELDA software estimated that 1.45 − 4.15% of Capan-2 cells were tumourigenic. These findings collectively imply that CD44+CD24+CD133+ subpopulation is potentially pCSCs, which survive chemotherapy and initiate recurrence. Capan-2 tumourspheres demonstrated molecular features of pCSCs as reported previously. GLI1 expression was down-regulated in these tumourspheres, suggesting an independence of canonical Hedgehog signaling. This finding explains an unexpectedly moderate response of CD44+CD24+CD133+ cells (p=0.738) and tumourspheres (IC50>20µM) to vismodegib treatment that targets canonical Hedgehog signaling. The integrity of tumourspheres was remarkably irresponsive to gemcitabine (IC50>100µM), which is in line with an enrichment of CD44+CD24+CD133+ subpopulation (p=0.002). Conclusion Capan-2 human pancreatic cancer cell line harbours CD44+CD24+CD133+ subpopulation that behaves like pCSCs, thus it is an attractive substitute for patients’ tumour biopsies for anti-pCSC drug discovery. Keywords: pancreatic cancer stem cells, chemoresistance, Hedgehog signaling, Tumourigenicity, Pancreatic cancer cell lines Conference: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”, Putrajaya, Malaysia, 3 Dec - 5 Feb, 2019. Presentation Type: Oral Presentation Topic: Cancer Citation: Teh Y, Ramasamy R and Stanslas J (2019). Controversial truth: human pancreatic cancer cell line homes cancer stem cells. Front. Pharmacol. Conference Abstract: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”. doi: 10.3389/conf.fphar.2018.63.00061 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 22 Sep 2018; Published Online: 17 Jan 2019. * Correspondence: Prof. Johnson Stanslas, Department of Medicine, Faculty of Medicine and Health Sciences, University Putra Malaysia, Serdang, Malaysia, jstanslas@yahoo.co.uk Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Yuan Han Teh Rajesh Ramasamy Johnson Stanslas Google Yuan Han Teh Rajesh Ramasamy Johnson Stanslas Google Scholar Yuan Han Teh Rajesh Ramasamy Johnson Stanslas PubMed Yuan Han Teh Rajesh Ramasamy Johnson Stanslas Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.