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 journalArticle

82 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)2088-2099
Number of pages12
JournalCell Reports
Volume3
Issue number6
DOIs
StatePublished - Mar 27 2013
Externally publishedYes

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Induced Pluripotent Stem Cells
Stem cells
Pancreatic Neoplasms
Adenocarcinoma
Cells
Cell Line
Genes
Neoplasms
Tissue
Disease Progression
Proteins
Genotype
Technology

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

An iPSC Line from Human Pancreatic Ductal Adenocarcinoma Undergoes Early to Invasive Stages of Pancreatic Cancer Progression. / Kim, Jungsun; Hoffman, John P.; Alpaugh, R. Katherine; Rhimm, Andrew D.; Reichert, Maximilian; Stanger, Ben Z.; Furth, Emma E.; Sepulveda, Antonia R.; Yuan, Chao Xing; Won, Kyoung Jae; Donahue, Greg; Sands, Jessica; Gumbs, Andrew A.; Zaret, Kenneth S.

In: Cell Reports, Vol. 3, No. 6, 27.03.2013, p. 2088-2099.

Research output: Contribution to journalArticle

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
Kim, Jungsun ; Hoffman, John P. ; Alpaugh, R. Katherine ; Rhimm, Andrew D. ; Reichert, Maximilian ; Stanger, Ben Z. ; Furth, Emma E. ; Sepulveda, Antonia R. ; Yuan, Chao Xing ; Won, Kyoung Jae ; Donahue, Greg ; Sands, Jessica ; Gumbs, Andrew A. ; Zaret, Kenneth S. / An iPSC Line from Human Pancreatic Ductal Adenocarcinoma Undergoes Early to Invasive Stages of Pancreatic Cancer Progression. In: Cell Reports. 2013 ; Vol. 3, No. 6. pp. 2088-2099.
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