title: FoxO1-negative cells are cancer stem-like cells in pancreatic ductal adenocarcinoma.
abstract: Flow cytometry assays using aldehyde dehydrogenase (ALDH) activity or CD133 positivity to isolate cancer stem cells (CSCs) are widely applied but have limitations. Thus, characterization of CSC makers for a specific cancer is potentially important. We have previously shown that miR-21 regulates cancer cell growth via FoxO1 in pancreatic ductal adenocarcinoma (PDAC). Here, we areported evidence of FoxO1-negative PDAC cells as CSCs in PDAC. Both ALDH-high and CD133-high cell fractions isolated from PDAC of the patients expressed high levels of miR-21 and null FoxO1. Cultured PDAC cells were virally transduced with GFP under FoxO1 promoter. GFP (FoxO1)-null PDAC cells expressed high levels of miR-21, and grew more quickly than FoxO1-positive PDAC cells. Moreover, the fold increases in growth of FoxO1-negative vs FoxO1-positive cells were greater than CD133-high vs CD133-low cells, or ALDH-high vs ALDH-low cells. Further, FoxO1-negative cells formed tumor spheres in culture and developed tumors after serial adoptive transplantation into NOD/SCID mice, while the FoxO1-positive cells did not. Finally, selective elimination of FoxO1-negative cells completely inhibited the growth of PDAC cells. Together, these data suggest that FoxO1-negative cells as CSCs in PDAC, and targeting FoxO1-negative cells in PDAC may provide better therapeutic outcome.
authors.affiliation: 1] Department of Medical Oncology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, China [2] Shanghai Key Laboratory of Pancreatic Diseases Research, Shanghai 200080, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Song
authors.affiliation: 1] Department of Medical Oncology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, China [2] Shanghai Key Laboratory of Pancreatic Diseases Research, Shanghai 200080, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, China.
authors.forename: Weiyi
authors.initials: W
authors.lastname: Huang
authors.affiliation: 1] Department of Medical Oncology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, China [2] Shanghai Key Laboratory of Pancreatic Diseases Research, Shanghai 200080, China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D064593:Heterografts; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism
chemical_list: C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D012334:RNA, Neoplasm