An iPSC line from human pancreatic ductal adenocarcinoma undergoes early to invasive stages of pancreatic cancer progression

Jungsun Kim; John P Hoffman; R Katherine Alpaugh; Andrew D Rhim; Andrew D Rhimm; Maximilian Reichert; Ben Z Stanger; Emma E Furth; Antonia R Sepulveda; Chao-Xing Yuan; Kyoung-Jae Won; Greg Donahue; Jessica Sands; Andrew A Gumbs; Kenneth S Zaret

doi:10.1016/j.celrep.2013.05.036

An iPSC line from human pancreatic ductal adenocarcinoma undergoes early to invasive stages of pancreatic cancer progression

Jungsun Kim, John P Hoffman, R Katherine Alpaugh, Andrew D Rhim, Andrew D Rhimm, Maximilian Reichert, Ben Z Stanger, Emma E Furth, Antonia R Sepulveda, Chao-Xing Yuan, Kyoung-Jae Won, Greg Donahue, Jessica Sands, Andrew A Gumbs, Kenneth S Zaret

96 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Cell Reports
Vol/bind	3
Udgave nummer	6
Sider (fra-til)	2088-99
Antal sider	12
ISSN	2211-1247
DOI	https://doi.org/10.1016/j.celrep.2013.05.036
Status	Udgivet - 27 mar. 2013
Udgivet eksternt	Ja

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10.1016/j.celrep.2013.05.036Licens: CC BY-NC-ND

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Kim, J., Hoffman, J. P., Alpaugh, R. K., Rhim, A. D., Rhimm, A. D., Reichert, M., Stanger, B. Z., Furth, E. E., Sepulveda, A. R., Yuan, C-X., Won, K-J., Donahue, G., Sands, J., Gumbs, A. A., & Zaret, K. S. (2013). An iPSC line from human pancreatic ductal adenocarcinoma undergoes early to invasive stages of pancreatic cancer progression. Cell Reports, 3(6), 2088-99. https://doi.org/10.1016/j.celrep.2013.05.036

Kim, J, Hoffman, JP, Alpaugh, RK, Rhim, AD, Rhimm, AD, Reichert, M, Stanger, BZ, Furth, EE, Sepulveda, AR, Yuan, C-X, Won, K-J, Donahue, G, Sands, J, Gumbs, AA & Zaret, KS 2013, 'An iPSC line from human pancreatic ductal adenocarcinoma undergoes early to invasive stages of pancreatic cancer progression', Cell Reports, bind 3, nr. 6, s. 2088-99. https://doi.org/10.1016/j.celrep.2013.05.036

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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. ",

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author = "Jungsun Kim and Hoffman, {John P} and Alpaugh, {R Katherine} and Rhim, {Andrew D} and Rhimm, {Andrew D} and Maximilian Reichert and Stanger, {Ben Z} and Furth, {Emma E} and Sepulveda, {Antonia R} and Chao-Xing Yuan and Kyoung-Jae Won and Greg Donahue and Jessica Sands and Gumbs, {Andrew A} and Zaret, {Kenneth S}",

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doi = "10.1016/j.celrep.2013.05.036",

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AU - Kim, Jungsun

AU - Hoffman, John P

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AU - Rhim, Andrew D

AU - Rhimm, Andrew D

AU - Reichert, Maximilian

AU - Stanger, Ben Z

AU - Furth, Emma E

AU - Sepulveda, Antonia R

AU - Yuan, Chao-Xing

AU - Won, Kyoung-Jae

AU - Donahue, Greg

AU - Sands, Jessica

AU - Gumbs, Andrew A

AU - Zaret, Kenneth S

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N2 - 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.

AB - 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.

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KW - Disease Progression

KW - Female

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Induced Pluripotent Stem Cells/pathology

KW - Mice

KW - Mice, Inbred NOD

KW - Mice, SCID

KW - Neoplastic Stem Cells/pathology

KW - Pancreatic Neoplasms/genetics

KW - Precancerous Conditions/genetics

KW - Prognosis

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JO - Cell Reports

JF - Cell Reports

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An iPSC line from human pancreatic ductal adenocarcinoma undergoes early to invasive stages of pancreatic cancer progression

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