Abstract
Pancreatic cancer stem cells (CSCs) play a crucial role in tumorigenesis and chemoresistance of pancreatic ductal adenocarcinoma. Pancreatic adenocarcinoma up-regulated factor (PAUF), a novel secretory protein, has been shown to contribute to cancer progression and metastasis. Because the clinical relationship between PAUF and pancreatic CSCs is largely unknown, we investigated the associations between the functional role of PAUF and pancreatic CSCs. Pancreatic cancer sphere cultured from the CFPAC-1 cells showed elevated expression of PAUF and pluripotent stemness genes (Oct4, Nanog, Stat3, and Sox2), and the mRNA of PAUF were increased in CD44+CD24+ESA+ pancreatic CSCs. PAUF knockdown (shPAUF) CFPAC-1 diminished the number of spheres and decreased stemness genes and CSC surface markers (CD133, c-MET and ALDH1). In addition, siPAUF CFPAC-1 decreased the mRNA expression of multidrug resistant protein 5 (MRP5) and ribonucleotide reductase M2 (RRM2) and were more vulnerable to gemcitabine and 5-FU than negative control (p<0.05). In conclusion, PAUF was increased in pancreatic CSCs and the suppression of PAUF enhances chemotherapeutic response to gemcitabine and 5FU by decreasing MRP5 and RRM2 in pancreatic cancer cells.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies and is the fourth leading cause of cancer-related death in the western world [1, 2]
Recent studies have demonstrated the presence of pancreatic cancer stem cells (CSCs), which are capable of self-renewal and production of differentiated progeny, in PDAC
The above-mentioned studies suggest functional roles of Pancreatic adenocarcinoma up-regulated factor (PAUF) in pancreatic cancer; little is known about the clinical relationship between PAUF and pancreatic CSCs
Summary
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies and is the fourth leading cause of cancer-related death in the western world [1, 2]. Li et al has identified populations of CSCs in PDAC that express the cell surface markers CD44+CD24+ESA+or c-Met [3, 4] Apart from these markers, CD133+ and ALDH1 are regarded as other markers of CSCs in PDAC [5,6,7]. These CSCs are characterized by their chemoresistance, as CD133+ pancreatic cancer cells have greater drug resistance to gemcitabine [6], and c-MET inhibitors have been shown to enhance antitumor effects in combination with gemcitabine [3]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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 callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
