title: An iPSC line from human pancreatic ductal adenocarcinoma undergoes early to invasive stages of pancreatic cancer progression.
abstract: Pancreatic ductal adenocarcinoma (PDAC) carries a dismal prognosis and lacks a human cell model of early disease progression. When human PDAC cells are injected into immunodeficient mice, they generate advanced-stage cancer. We hypothesized that if human PDAC cells were converted to pluripotency and then allowed to differentiate back into pancreatic tissue, they might undergo early stages of cancer. Although most induced pluripotent stem cell (iPSC) lines were not of the expected cancer genotype, one PDAC line, 10-22 cells, when injected into immunodeficient mice, generated pancreatic intraepithelial neoplasia (PanIN) precursors to PDAC that progressed to the invasive stage. The PanIN-like cells secrete or release proteins from many genes that are known to be expressed in human pancreatic cancer progression and that predicted an HNF4α network in intermediate-stage lesions. Thus, rare events allow iPSC technology to provide a live human cell model of early pancreatic cancer and insights into disease progression.
authors.affiliation: Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-5157, USA.
authors.forename: Jungsun
authors.initials: J
authors.lastname: Kim
authors.forename: John P
authors.initials: JP
authors.lastname: Hoffman
authors.forename: R Katherine
authors.initials: RK
authors.lastname: Alpaugh
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Rhim
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Rhimm
authors.forename: Maximilian
authors.initials: M
authors.lastname: Reichert
authors.forename: Ben Z
authors.initials: BZ
authors.lastname: Stanger
authors.forename: Emma E
authors.initials: EE
authors.lastname: Furth
authors.forename: Antonia R
authors.initials: AR
authors.lastname: Sepulveda
authors.forename: Chao-Xing
authors.initials: CX
authors.lastname: Yuan
authors.forename: Kyoung-Jae
authors.initials: KJ
authors.lastname: Won
authors.forename: Greg
authors.initials: G
authors.lastname: Donahue
authors.forename: Jessica
authors.initials: J
authors.lastname: Sands
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Gumbs
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Zaret
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002417:Cattle; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor