Abstract
Pancreatic ductal adenocarcinoma is highly resistant to systemic chemotherapy. Although there are many reports using pancreatic cancer cells derived from patients who did not receive chemotherapy, characteristics of pancreatic cancer cells from chemotherapy-resistant patients remain unclear. In this study, we set out to establish a cancer cell line in disseminated cancer cells derived from gemcitabine-resistant pancreatic ductal adenocarcinoma patients. By use of in vitro co-culture system with stromal cells, we established a novel pancreatic tumor-initiating cell line. The cell line required its direct interaction with stromal cells for its in vitro clonogenic growth and passaging. Their direct interaction induced basal lamina-like extracellular matrix formation that maintained colony formation. The cell line expressed CD133 protein, which expression level changed autonomously and by culture conditions. These results demonstrated that there were novel pancreatic tumor-initiating cells that required direct interactions with stromal cells for their in vitro cultivation in gemcitabine-resistant pancreatic ductal adenocarcinoma. This cell line would help to develop novel therapies that enhance effects of gemcitabine or novel anti-cancer drugs.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a high cancer dissemination rate, which results in high mortality [1]
These results demonstrate that KMC14 cells are pancreatic tumor-initiating cells
When a single KMC14-cell suspension was cultured on the Synthesized Basement Membrane (sBM), there was no colony observed. These results demonstrate that KMC14 cells induce basal lamina-like extracellular matrix (ECM) formation via stromal cells that maintains KMC14 colony formation
Summary
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a high cancer dissemination rate, which results in high mortality [1]. The majority of PDAC patients already have either locally advanced or metastatic cancer, when the patients aware symptoms. They are treated with mainly gemcitabine- or fluorouracil-based systemic chemotherapy [2,3]. It is conceivable that characterizations of carcinoma cells derived from gemcitabine-resistant PDAC patients are useful. Such cell lines, have not been established, because adjuvant chemotherapy before surgical resection is not common for PDAC and PDAC cell lines reported in previous papers are generally from surgical specimen of PDAC patients who did not receive chemotherapy [6,7,8,9,10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
