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. 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. 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

Research output: Contribution to journal › Article › peer-review

138 Scopus citations

Abstract

Pancreatic ductal adenocarcinoma (PDAC) carries a dismal prognosis and lacks a human cell model ofearly 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.

Original language	English (US)
Pages (from-to)	2088-2099
Number of pages	12
Journal	Cell Reports
Volume	3
Issue number	6
DOIs	https://doi.org/10.1016/j.celrep.2013.05.036
State	Published - Mar 27 2013
Externally published	Yes

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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Kim, J., Hoffman, J. P., Alpaugh, R. K., 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), 2088-2099. https://doi.org/10.1016/j.celrep.2013.05.036

Kim, J, Hoffman, JP, Alpaugh, RK, Rhimm, AD, Reichert, M, Stanger, BZ, Furth, EE, Sepulveda, AR, Yuan, CX, Won, KJ, 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, vol. 3, no. 6, pp. 2088-2099. 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 ofearly 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.",

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

note = "Funding Information: We thank the patients who donated their tissue for this study and T. Jiang, G. Swan, T. Secreto; C. Keeper for technical assistance; A. Rustgi, J. Gearhart, M. Grompe, and D. Metzger for comments on the manuscript; and E. Hulme for help with the manuscript. We thank the UPenn Stem Cell and Xenograft Core, Proteomics Core (NIH P30CA016520, AFCRE and ES013508-04, CEET) and MPI Core of the Center for Molecular Studies in Digestive and Liver Diseases (NIH/NIDDK P30-DK050306). The work was funded by NIH MERIT Award R37GM36477 to K.S.Z. This work is presented in memory of J.M. ",

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month = mar,

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

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AU - Kim, Jungsun

AU - Hoffman, John P.

AU - Alpaugh, R. Katherine

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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PY - 2013/3/27

Y1 - 2013/3/27

N2 - Pancreatic ductal adenocarcinoma (PDAC) carries a dismal prognosis and lacks a human cell model ofearly 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 ofearly 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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An iPSC Line from Human Pancreatic Ductal Adenocarcinoma Undergoes Early to Invasive Stages of Pancreatic Cancer Progression

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