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Pancreatic Acinar-to-Ductal Metaplasia and Pancreatic Cancer

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Pancreatic Cancer

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1882))

Abstract

Acinar-to-ductal metaplasia (ADM) of the pancreas is a process that pancreatic acinar cells differentiate into ductal-like cells with ductal cell traits. The metaplasia of pancreatic acinar cells manifests their ability to adapt to the genetic and environmental pressure they encounter. However, with oncogenic genetic insults and/or sustained environmental stress, ADM may lead to pancreatic intraepithelial neoplasia (PanIN), which is a common precancerous lesion that precedes pancreatic cancer. Understanding the intermediate states of ADM and important molecules that regulate ADM formation may help the development of novel preventive strategies that could be translated to the clinic to benefit the people with high risk of pancreatic cancer. Mouse model is widely used in both in vivo and ex vivo studies of ADM. In this chapter, we describe detailed protocols of injury models of the adult mouse pancreas that can function as a tool to study mechanisms of ADM formation.

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References

  1. Siegel RL, Miller KD, Jemal A (2017) Cancer statistics, 2017. CA Cancer J Clin 67:7–30

    Article  Google Scholar 

  2. Bockman DE, Guo J, Buchler P, Muller MW, Bergmann F, Friess H (2003) Origin and development of the precursor lesions in experimental pancreatic cancer in rats. Laboratory Investigation 83:853–859

    Article  Google Scholar 

  3. Gidekel Friedlander SY, Chu GC, Snyder EL, Girnius N, Dibelius G, Crowley D, Vasile E, DePinho RA, Jacks T (2009) Context-dependent transformation of adult pancreatic cells by oncogenic K-Ras. Cancer Cell 16:379–389

    Article  Google Scholar 

  4. Bardeesy N, DePinho RA (2002) Pancreatic cancer biology and genetics. Nat Rev Cancer 2:897–909

    Article  CAS  Google Scholar 

  5. Kopp JL, von Figura G, Mayes E, Liu FF, Dubois CL, Morris JPT, Pan FC, Akiyama H, Wright CV, Jensen K, Hebrok M, Sander M (2012) Identification of Sox9-dependent acinar-to-ductal reprogramming as the principal mechanism for initiation of pancreatic ductal adenocarcinoma. Cancer Cell 22:737–750

    Article  CAS  Google Scholar 

  6. Wei D, Wang L, Yan Y, Jia Z, Gagea M, Li Z, Zuo X, Kong X, Huang S, Xie K (2016) KLF4 is essential for induction of cellular identity change and acinar-to-ductal reprogramming during early pancreatic carcinogenesis. Cancer Cell 29:324–338

    Article  CAS  Google Scholar 

  7. Strobel O, Dor Y, Alsina J, Stirman A, Lauwers G, Trainor A, Castillo CF, Warshaw AL, Thayer SP (2007) In vivo lineage tracing defines the role of acinar-to-ductal transdifferentiation in inflammatory ductal metaplasia. Gastroenterology 133:1999–2009

    Article  Google Scholar 

  8. Shi G, DiRenzo D, Qu C, Barney D, Miley D, Konieczny SF (2013) Maintenance of acinar cell organization is critical to preventing Kras-induced acinar-ductal metaplasia. Oncogene 32:1950–1958

    Article  CAS  Google Scholar 

  9. Prevot PP, Simion A, Grimont A, Colletti M, Khalaileh A, Van den Steen G, Sempoux C, Xu X, Roelants V, Hald J, Bertrand L, Heimberg H, Konieczny SF, Dor Y, Lemaigre FP, Jacquemin P (2012) Role of the ductal transcription factors HNF6 and Sox9 in pancreatic acinar-to-ductal metaplasia. Gut 61:1723–1732

    Article  CAS  Google Scholar 

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Acknowledgments

We thank Professor Keping Xie for support. This work was supported in part by grants R01-CA129956, R01-CA148954, R01-CA152309, R01-CA172233, R01-CA195651, R01-CA198090, and R01CA220236 from the National Cancer Institute, National Institutes of Health, and from the M.D. Anderson Cancer Center Institutional Research program. All authors disclose no conflicts of interest.

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Correspondence to Daoyan Wei .

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Wang, L., Xie, D., Wei, D. (2019). Pancreatic Acinar-to-Ductal Metaplasia and Pancreatic Cancer. In: Su, G. (eds) Pancreatic Cancer. Methods in Molecular Biology, vol 1882. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8879-2_26

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  • DOI: https://doi.org/10.1007/978-1-4939-8879-2_26

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-8878-5

  • Online ISBN: 978-1-4939-8879-2

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