title: LIN28B suppresses microRNA let-7b expression to promote CD44+/LIN28B+ human pancreatic cancer stem cell proliferation and invasion.
abstract: Although the highly proliferative, migratory, and multi-drug resistant phenotype of human pancreatic cancer stem cells (PCSCs) is well characterized, knowledge of their biological mechanisms is limited. We used CD44 and LIN28B as markers to screen, isolate, and enrich CSCs from human primary pancreatic cancer. Using flow cytometry, we identified a human primary pancreatic cancer cell (PCC) subpopulation expressing high levels of both CD44 and LIN28B. CD44+/LIN28B+ PCSCs expressed high levels of stemness marker genes and possessed higher migratory and invasive ability than CD44-/LIN28B- PCCs. CD44+/LIN28B+ PCSCs were more resistant to growth inhibition induced by the chemotherapeutic drugs cisplatin and gemcitabine hydrochloride, and readily established tumors in vivo in a relatively short time. Moreover, microarray analysis revealed significant differences between the cDNA expression patterns of CD44+/LIN28B+ PCSCs and CD44-/LIN28B- PCCs. Following siRNA interference of endogenous LIN28B gene expression in CD44+/LIN28B+ PCSCs, not only was their proliferation decreased, there was also cell cycle arrest due to suppression of cyclin D1 expression following the stimulation of miRNA let-7b expression. In conclusion, CD44+/LIN28B+ cells, which possess CSC characteristics, can be reliably sorted from human primary PCCs and represent a valuable model for studying cancer cell physiology and multi-drug resistance.
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University Shanghai 200032, China.
authors.forename: Yebo
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University Shanghai 200032, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Jiangsu University Affiliated Hospital Zhengjiang 212000, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cui
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University Shanghai 200032, China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Lou
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University Shanghai 200032, China.
authors.forename: Dansong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University Shanghai 200032, China.
authors.forename: Weiqi
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University Shanghai 200032, China.
authors.forename: Dayong
authors.initials: D
authors.lastname: Jin
authors.affiliation: Shanghai Geriatric Institute of Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine Shanghai 200031, China.
authors.forename: Te
authors.initials: T
authors.lastname: Liu
keywords: CD44; LIN28B; Pancreatic ductal adenocarcinoma; cancer stem cells