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- W1220654018 abstract "Pancreatic ductal adenocarcinoma (PDAC) has one of the worst prognoses of any human malignancy. When human PDAC cells are injected into immunodeficient animals, they create tumors of the late stage from which they were derived. 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 that we generated from PDAC were not of the expected cancer genotype, one PDAC iPS-like line, 10–22 cells, conferred the highly disrupted cancer genome of the starting tumor epithelial population. When 10-22 iPS-like cells are injected into immunodeficient mice, they generate pancreatic intraepithelial neoplasia (PanIN) precursors that progress to the invasive stage PDAC. Using this unique system, we established serum-free cultures of human PanIN lesions from immunodeficient mice injected with 10-22 cells and analyzed the proteome of secreted and released proteins. The live human PanIN explants secrete or release proteins from many genes that are known to be expressed in human pancreatic cancer progression and that predicted an HNF4a network achieved in intermediate-stage lesions from new clinical samples. Recent studies show that the PanIN cells progress to metastases at longer time. The 10-22 cell line is being engineered with near-infrared fluorescent protein under the control of the ductal K19 promoter so that populations can be retrieved by FACS for transcriptome analysis as well as tumor progression and regression in response to drugs can be monitored in vivo. We are now assessing the secreted or released proteins from early lesions grown in mice as diagnostic markers for human PDAC prognosis. Thus, rare events allow iPSC technology to provide a live human cell model of early pancreatic cancer and insights into disease progression. Citation Format: Jungsun Kim, Kenneth S. Zaret. Modeling of early to invasive stages of pancreatic cancer progression with an iPSC-like line from human pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B116." @default.
- W1220654018 created "2016-06-24" @default.
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- W1220654018 date "2015-06-30" @default.
- W1220654018 modified "2023-09-26" @default.
- W1220654018 title "Abstract B116: Modeling of early to invasive stages of pancreatic cancer progression with an iPSC-like line from human pancreatic ductal adenocarcinoma" @default.
- W1220654018 doi "https://doi.org/10.1158/1538-7445.panca2014-b116" @default.
- W1220654018 hasPublicationYear "2015" @default.
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