Skip to main content
Erschienen in: Surgery Today 1/2018

04.03.2017 | Review Article

Cells of origin of pancreatic neoplasms

verfasst von: Junpei Yamaguchi, Yukihiro Yokoyama, Toshio Kokuryo, Tomoki Ebata, Masato Nagino

Erschienen in: Surgery Today | Ausgabe 1/2018

Einloggen, um Zugang zu erhalten

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignant disease associated with poor prognosis, despite recent medical advances. It is of great importance to understand the initial events and cells of origin of pancreatic cancer to prevent the development and progression of PDAC. There are three distinct precursor lesions that develop into PDAC: pancreatic intraepithelial neoplasms (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and mucinous cystic neoplasms (MCNs). Studies on genetically engineered mouse models have revealed that the initiation and development of these lesions largely depend on genetic alterations. These lesions originate from different populations in the pancreas. PanIN development seems to be the result of the transdifferentiation of acinar cells, whereas IPMNs most likely arise from the progenitor niche of the pancreatic ductal epithelium. Pancreatic carcinogenesis is dependent on various events, including gene alterations, environmental insults, and cell types. However, further studies are needed to fully understand the initial processes of pancreatic cancer.
Literatur
2.
Zurück zum Zitat Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P, et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 2008;321:1801–6.CrossRefPubMedPubMedCentral Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P, et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 2008;321:1801–6.CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Morris JPt, Wang SC, Hebrok M. KRAS, Hedgehog. Wnt and the twisted developmental biology of pancreatic ductal adenocarcinoma. Nat Rev Cancer. 2010;10:683–95.CrossRefPubMedPubMedCentral Morris JPt, Wang SC, Hebrok M. KRAS, Hedgehog. Wnt and the twisted developmental biology of pancreatic ductal adenocarcinoma. Nat Rev Cancer. 2010;10:683–95.CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat Kanda M, Matthaei H, Wu J, Hong SM, Yu J, Borges M, et al. Presence of somatic mutations in most early-stage pancreatic intraepithelial neoplasia. Gastroenterology 2012;142:730 e9–733 e9.CrossRef Kanda M, Matthaei H, Wu J, Hong SM, Yu J, Borges M, et al. Presence of somatic mutations in most early-stage pancreatic intraepithelial neoplasia. Gastroenterology 2012;142:730 e9–733 e9.CrossRef
5.
Zurück zum Zitat Hruban RH, Goggins M, Parsons J, Kern SE. Progression model for pancreatic cancer. Clin Cancer Res. 2000;6:2969–72.PubMed Hruban RH, Goggins M, Parsons J, Kern SE. Progression model for pancreatic cancer. Clin Cancer Res. 2000;6:2969–72.PubMed
6.
Zurück zum Zitat Lohr M, Kloppel G, Maisonneuve P, Lowenfels AB, Luttges J. Frequency of K-ras mutations in pancreatic intraductal neoplasias associated with pancreatic ductal adenocarcinoma and chronic pancreatitis: a meta-analysis. Neoplasia. 2005;7:17–23.CrossRefPubMedPubMedCentral Lohr M, Kloppel G, Maisonneuve P, Lowenfels AB, Luttges J. Frequency of K-ras mutations in pancreatic intraductal neoplasias associated with pancreatic ductal adenocarcinoma and chronic pancreatitis: a meta-analysis. Neoplasia. 2005;7:17–23.CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Koorstra JB, Feldmann G, Habbe N, Maitra A. Morphogenesis of pancreatic cancer: role of pancreatic intraepithelial neoplasia (PanINs). Langenbecks Arch Surg. 2008;393:561–70.CrossRefPubMedPubMedCentral Koorstra JB, Feldmann G, Habbe N, Maitra A. Morphogenesis of pancreatic cancer: role of pancreatic intraepithelial neoplasia (PanINs). Langenbecks Arch Surg. 2008;393:561–70.CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Lowenfels AB, Maisonneuve P, Cavallini G, Ammann RW, Lankisch PG, Andersen JR, et al. Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group. N Engl J Med. 1993;328:1433–7.CrossRefPubMed Lowenfels AB, Maisonneuve P, Cavallini G, Ammann RW, Lankisch PG, Andersen JR, et al. Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group. N Engl J Med. 1993;328:1433–7.CrossRefPubMed
9.
Zurück zum Zitat Westphalen CB, Takemoto Y, Tanaka T, Macchini M, Jiang Z, Renz BW, et al. Dclk1 defines quiescent pancreatic progenitors that promote injury-induced regeneration and tumorigenesis. Cell Stem Cell. 2016;18:441–55.CrossRefPubMedPubMedCentral Westphalen CB, Takemoto Y, Tanaka T, Macchini M, Jiang Z, Renz BW, et al. Dclk1 defines quiescent pancreatic progenitors that promote injury-induced regeneration and tumorigenesis. Cell Stem Cell. 2016;18:441–55.CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Yanagisawa A, Ohtake K, Ohashi K, Hori M, Kitagawa T, Sugano H, et al. Frequent c-Ki-ras oncogene activation in mucous cell hyperplasias of pancreas suffering from chronic inflammation. Cancer Res. 1993;53:953–6.PubMed Yanagisawa A, Ohtake K, Ohashi K, Hori M, Kitagawa T, Sugano H, et al. Frequent c-Ki-ras oncogene activation in mucous cell hyperplasias of pancreas suffering from chronic inflammation. Cancer Res. 1993;53:953–6.PubMed
11.
Zurück zum Zitat Guerra C, Schuhmacher AJ, Canamero M, Grippo PJ, Verdaguer L, Perez-Gallego L, et al. Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice. Cancer Cell. 2007;11:291–302.CrossRefPubMed Guerra C, Schuhmacher AJ, Canamero M, Grippo PJ, Verdaguer L, Perez-Gallego L, et al. Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice. Cancer Cell. 2007;11:291–302.CrossRefPubMed
12.
Zurück zum Zitat Hermann PC, Sancho P, Canamero M, Martinelli P, Madriles F, Michl P, et al. Nicotine promotes initiation and progression of KRAS-induced pancreatic cancer via Gata6-dependent dedifferentiation of acinar cells in mice. Gastroenterology 2014;147:1119 e4–1133 e4.CrossRef Hermann PC, Sancho P, Canamero M, Martinelli P, Madriles F, Michl P, et al. Nicotine promotes initiation and progression of KRAS-induced pancreatic cancer via Gata6-dependent dedifferentiation of acinar cells in mice. Gastroenterology 2014;147:1119 e4–1133 e4.CrossRef
13.
Zurück zum Zitat Blackford A, Parmigiani G, Kensler TW, Wolfgang C, Jones S, Zhang X, et al. Genetic mutations associated with cigarette smoking in pancreatic cancer. Cancer Res. 2009;69:3681–8.CrossRefPubMedPubMedCentral Blackford A, Parmigiani G, Kensler TW, Wolfgang C, Jones S, Zhang X, et al. Genetic mutations associated with cigarette smoking in pancreatic cancer. Cancer Res. 2009;69:3681–8.CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Katayama H, Kurokawa Y, Nakamura K, Ito H, Kanemitsu Y, Masuda N, et al. Extended Clavien–Dindo classification of surgical complications: Japan Clinical Oncology Group postoperative complications criteria. Surg Today. 2016;46:668–85.CrossRefPubMed Katayama H, Kurokawa Y, Nakamura K, Ito H, Kanemitsu Y, Masuda N, et al. Extended Clavien–Dindo classification of surgical complications: Japan Clinical Oncology Group postoperative complications criteria. Surg Today. 2016;46:668–85.CrossRefPubMed
15.
Zurück zum Zitat Tomihara H, Eguchi H, Yamada D, Gotoh K, Kawamoto K, Wada H, et al. Preoperative chemoradiotherapy does not compromise the feasibility of adjuvant chemotherapy for patients with pancreatic ductal adenocarcinoma. Surg Today. 2017;47:218–26.CrossRefPubMed Tomihara H, Eguchi H, Yamada D, Gotoh K, Kawamoto K, Wada H, et al. Preoperative chemoradiotherapy does not compromise the feasibility of adjuvant chemotherapy for patients with pancreatic ductal adenocarcinoma. Surg Today. 2017;47:218–26.CrossRefPubMed
16.
Zurück zum Zitat Koo BK, Clevers H. Stem cells marked by the R-spondin receptor LGR5. Gastroenterology. 2014;147:289–302.CrossRefPubMed Koo BK, Clevers H. Stem cells marked by the R-spondin receptor LGR5. Gastroenterology. 2014;147:289–302.CrossRefPubMed
18.
Zurück zum Zitat Barker N, Clevers H. Leucine-rich repeat-containing G-protein-coupled receptors as markers of adult stem cells. Gastroenterology. 2010;138:1681–96.CrossRefPubMed Barker N, Clevers H. Leucine-rich repeat-containing G-protein-coupled receptors as markers of adult stem cells. Gastroenterology. 2010;138:1681–96.CrossRefPubMed
20.
Zurück zum Zitat Tian H, Biehs B, Warming S, Leong KG, Rangell L, Klein OD, et al. A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable. Nature. 2011;478:255–9.CrossRefPubMedPubMedCentral Tian H, Biehs B, Warming S, Leong KG, Rangell L, Klein OD, et al. A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable. Nature. 2011;478:255–9.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature. 2007;449:1003–7.CrossRefPubMed Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature. 2007;449:1003–7.CrossRefPubMed
22.
Zurück zum Zitat Scoville DH, Sato T, He XC, Li L. Current view: intestinal stem cells and signaling. Gastroenterology. 2008;134:849–64.CrossRefPubMed Scoville DH, Sato T, He XC, Li L. Current view: intestinal stem cells and signaling. Gastroenterology. 2008;134:849–64.CrossRefPubMed
23.
Zurück zum Zitat Barker N, Bartfeld S, Clevers H. Tissue-resident adult stem cell populations of rapidly self-renewing organs. Cell Stem Cell. 2010;7:656–70.CrossRefPubMed Barker N, Bartfeld S, Clevers H. Tissue-resident adult stem cell populations of rapidly self-renewing organs. Cell Stem Cell. 2010;7:656–70.CrossRefPubMed
24.
25.
Zurück zum Zitat Morgan BA. The dermal papilla: an instructive niche for epithelial stem and progenitor cells in development and regeneration of the hair follicle. Cold Spring Harb Perspect Med. 2014;4:a015180.CrossRefPubMedPubMedCentral Morgan BA. The dermal papilla: an instructive niche for epithelial stem and progenitor cells in development and regeneration of the hair follicle. Cold Spring Harb Perspect Med. 2014;4:a015180.CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Chen CC, Plikus MV, Tang PC, Widelitz RB, Chuong CM. The modulatable stem cell niche: tissue interactions during hair and feather follicle regeneration. J Mol Biol. 2016;428:1423–40.CrossRefPubMed Chen CC, Plikus MV, Tang PC, Widelitz RB, Chuong CM. The modulatable stem cell niche: tissue interactions during hair and feather follicle regeneration. J Mol Biol. 2016;428:1423–40.CrossRefPubMed
27.
Zurück zum Zitat White AC, Lowry WE. Refining the role for adult stem cells as cancer cells of origin. Trends Cell Biol. 2015;25:11–20.CrossRefPubMed White AC, Lowry WE. Refining the role for adult stem cells as cancer cells of origin. Trends Cell Biol. 2015;25:11–20.CrossRefPubMed
30.
31.
Zurück zum Zitat Arwert EN, Hoste E, Watt FM. Epithelial stem cells, wound healing and cancer. Nat Rev Cancer. 2012;12:170–80.CrossRefPubMed Arwert EN, Hoste E, Watt FM. Epithelial stem cells, wound healing and cancer. Nat Rev Cancer. 2012;12:170–80.CrossRefPubMed
32.
Zurück zum Zitat Youssef KK, Van Keymeulen A, Lapouge G, Beck B, Michaux C, Achouri Y, et al. Identification of the cell lineage at the origin of basal cell carcinoma. Nat Cell Biol. 2010;12:299–305.PubMed Youssef KK, Van Keymeulen A, Lapouge G, Beck B, Michaux C, Achouri Y, et al. Identification of the cell lineage at the origin of basal cell carcinoma. Nat Cell Biol. 2010;12:299–305.PubMed
33.
Zurück zum Zitat Wang GY, Wang J, Mancianti ML, Epstein EH Jr. Basal cell carcinomas arise from hair follicle stem cells in Ptch1(+/−) mice. Cancer Cell. 2011;19:114–24.CrossRefPubMedPubMedCentral Wang GY, Wang J, Mancianti ML, Epstein EH Jr. Basal cell carcinomas arise from hair follicle stem cells in Ptch1(+/−) mice. Cancer Cell. 2011;19:114–24.CrossRefPubMedPubMedCentral
34.
Zurück zum Zitat Grachtchouk M, Pero J, Yang SH, Ermilov AN, Michael LE, Wang A, et al. Basal cell carcinomas in mice arise from hair follicle stem cells and multiple epithelial progenitor populations. J Clin Invest. 2011;121:1768–81.CrossRefPubMedPubMedCentral Grachtchouk M, Pero J, Yang SH, Ermilov AN, Michael LE, Wang A, et al. Basal cell carcinomas in mice arise from hair follicle stem cells and multiple epithelial progenitor populations. J Clin Invest. 2011;121:1768–81.CrossRefPubMedPubMedCentral
35.
Zurück zum Zitat Kasper M, Jaks V, Are A, Bergstrom A, Schwager A, Svard J, et al. Wounding enhances epidermal tumorigenesis by recruiting hair follicle keratinocytes. Proc Natl Acad Sci USA. 2011;108:4099–104.CrossRefPubMedPubMedCentral Kasper M, Jaks V, Are A, Bergstrom A, Schwager A, Svard J, et al. Wounding enhances epidermal tumorigenesis by recruiting hair follicle keratinocytes. Proc Natl Acad Sci USA. 2011;108:4099–104.CrossRefPubMedPubMedCentral
37.
Zurück zum Zitat Barker N, Ridgway RA, van Es JH, van de Wetering M, Begthel H, van den Born M, et al. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature. 2009;457:608–11.CrossRefPubMed Barker N, Ridgway RA, van Es JH, van de Wetering M, Begthel H, van den Born M, et al. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature. 2009;457:608–11.CrossRefPubMed
38.
Zurück zum Zitat Zhu L, Gibson P, Currle DS, Tong Y, Richardson RJ, Bayazitov IT, et al. Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation. Nature. 2009;457:603–7.CrossRefPubMed Zhu L, Gibson P, Currle DS, Tong Y, Richardson RJ, Bayazitov IT, et al. Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation. Nature. 2009;457:603–7.CrossRefPubMed
39.
Zurück zum Zitat Schwitalla S, Fingerle AA, Cammareri P, Nebelsiek T, Goktuna SI, Ziegler PK, et al. Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties. Cell. 2013;152:25–38.CrossRefPubMed Schwitalla S, Fingerle AA, Cammareri P, Nebelsiek T, Goktuna SI, Ziegler PK, et al. Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties. Cell. 2013;152:25–38.CrossRefPubMed
40.
Zurück zum Zitat Rovira M, Scott SG, Liss AS, Jensen J, Thayer SP, Leach SD. Isolation and characterization of centroacinar/terminal ductal progenitor cells in adult mouse pancreas. Proc Natl Acad Sci USA. 2010;107:75–80.CrossRefPubMed Rovira M, Scott SG, Liss AS, Jensen J, Thayer SP, Leach SD. Isolation and characterization of centroacinar/terminal ductal progenitor cells in adult mouse pancreas. Proc Natl Acad Sci USA. 2010;107:75–80.CrossRefPubMed
41.
Zurück zum Zitat Huch M, Dorrell C, Boj SF, van Es JH, Li VS, van de Wetering M, et al. In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. Nature. 2013;494:247–50.CrossRefPubMedPubMedCentral Huch M, Dorrell C, Boj SF, van Es JH, Li VS, van de Wetering M, et al. In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. Nature. 2013;494:247–50.CrossRefPubMedPubMedCentral
42.
Zurück zum Zitat Kopp JL, Dubois CL, Schaffer AE, Hao E, Shih HP, Seymour PA, et al. Sox9+ ductal cells are multipotent progenitors throughout development but do not produce new endocrine cells in the normal or injured adult pancreas. Development. 2011;138:653–65.CrossRefPubMedPubMedCentral Kopp JL, Dubois CL, Schaffer AE, Hao E, Shih HP, Seymour PA, et al. Sox9+ ductal cells are multipotent progenitors throughout development but do not produce new endocrine cells in the normal or injured adult pancreas. Development. 2011;138:653–65.CrossRefPubMedPubMedCentral
43.
Zurück zum Zitat Kopp JL, Grompe M, Sander M. Stem cells versus plasticity in liver and pancreas regeneration. Nat Cell Biol. 2016;18:238–45.CrossRefPubMed Kopp JL, Grompe M, Sander M. Stem cells versus plasticity in liver and pancreas regeneration. Nat Cell Biol. 2016;18:238–45.CrossRefPubMed
44.
Zurück zum Zitat Puri S, Folias AE, Hebrok M. Plasticity and dedifferentiation within the pancreas: development, homeostasis, and disease. Cell Stem Cell. 2015;16:18–31.CrossRefPubMed Puri S, Folias AE, Hebrok M. Plasticity and dedifferentiation within the pancreas: development, homeostasis, and disease. Cell Stem Cell. 2015;16:18–31.CrossRefPubMed
45.
Zurück zum Zitat Merrell AJ, Stanger BZ. Adult cell plasticity in vivo: de-differentiation and transdifferentiation are back in style. Nat Rev Mol Cell Biol. 2016;17:413–25.CrossRefPubMed Merrell AJ, Stanger BZ. Adult cell plasticity in vivo: de-differentiation and transdifferentiation are back in style. Nat Rev Mol Cell Biol. 2016;17:413–25.CrossRefPubMed
47.
Zurück zum Zitat Zhu L, Shi G, Schmidt CM, Hruban RH, Konieczny SF. Acinar cells contribute to the molecular heterogeneity of pancreatic intraepithelial neoplasia. Am J Pathol. 2007;171:263–73.CrossRefPubMedPubMedCentral Zhu L, Shi G, Schmidt CM, Hruban RH, Konieczny SF. Acinar cells contribute to the molecular heterogeneity of pancreatic intraepithelial neoplasia. Am J Pathol. 2007;171:263–73.CrossRefPubMedPubMedCentral
48.
Zurück zum Zitat Habbe N, Shi G, Meguid RA, Fendrich V, Esni F, Chen H, et al. Spontaneous induction of murine pancreatic intraepithelial neoplasia (mPanIN) by acinar cell targeting of oncogenic Kras in adult mice. Proc Natl Acad Sci USA. 2008;105:18913–8.CrossRefPubMedPubMedCentral Habbe N, Shi G, Meguid RA, Fendrich V, Esni F, Chen H, et al. Spontaneous induction of murine pancreatic intraepithelial neoplasia (mPanIN) by acinar cell targeting of oncogenic Kras in adult mice. Proc Natl Acad Sci USA. 2008;105:18913–8.CrossRefPubMedPubMedCentral
49.
Zurück zum Zitat Kopp JL, von Figura G, Mayes E, Liu FF, Dubois CL, Morris JPt, et al. Identification of Sox9-dependent acinar-to-ductal reprogramming as the principal mechanism for initiation of pancreatic ductal adenocarcinoma. Cancer Cell. 2012;22:737–50.CrossRefPubMedPubMedCentral Kopp JL, von Figura G, Mayes E, Liu FF, Dubois CL, Morris JPt, et al. Identification of Sox9-dependent acinar-to-ductal reprogramming as the principal mechanism for initiation of pancreatic ductal adenocarcinoma. Cancer Cell. 2012;22:737–50.CrossRefPubMedPubMedCentral
50.
Zurück zum Zitat Kong B, Michalski CW, Erkan M, Friess H, Kleeff J. From tissue turnover to the cell of origin for pancreatic cancer. Nat Rev Gastroenterol Hepatol. 2011;8:467–72.CrossRefPubMed Kong B, Michalski CW, Erkan M, Friess H, Kleeff J. From tissue turnover to the cell of origin for pancreatic cancer. Nat Rev Gastroenterol Hepatol. 2011;8:467–72.CrossRefPubMed
51.
Zurück zum Zitat Furuyama K, Kawaguchi Y, Akiyama H, Horiguchi M, Kodama S, Kuhara T, et al. Continuous cell supply from a Sox9-expressing progenitor zone in adult liver, exocrine pancreas and intestine. Nat Genet. 2011;43:34–41.CrossRefPubMed Furuyama K, Kawaguchi Y, Akiyama H, Horiguchi M, Kodama S, Kuhara T, et al. Continuous cell supply from a Sox9-expressing progenitor zone in adult liver, exocrine pancreas and intestine. Nat Genet. 2011;43:34–41.CrossRefPubMed
52.
Zurück zum Zitat Delacour A, Nepote V, Trumpp A, Herrera PL. Nestin expression in pancreatic exocrine cell lineages. Mech Dev. 2004;121:3–14.CrossRefPubMed Delacour A, Nepote V, Trumpp A, Herrera PL. Nestin expression in pancreatic exocrine cell lineages. Mech Dev. 2004;121:3–14.CrossRefPubMed
53.
Zurück zum Zitat Esni F, Stoffers DA, Takeuchi T, Leach SD. Origin of exocrine pancreatic cells from nestin-positive precursors in developing mouse pancreas. Mech Dev. 2004;121:15–25.CrossRefPubMed Esni F, Stoffers DA, Takeuchi T, Leach SD. Origin of exocrine pancreatic cells from nestin-positive precursors in developing mouse pancreas. Mech Dev. 2004;121:15–25.CrossRefPubMed
54.
Zurück zum Zitat Ishiwata T, Kudo M, Onda M, Fujii T, Teduka K, Suzuki T, et al. Defined localization of nestin-expressing cells in l-arginine-induced acute pancreatitis. Pancreas. 2006;32:360–8.CrossRefPubMed Ishiwata T, Kudo M, Onda M, Fujii T, Teduka K, Suzuki T, et al. Defined localization of nestin-expressing cells in l-arginine-induced acute pancreatitis. Pancreas. 2006;32:360–8.CrossRefPubMed
55.
Zurück zum Zitat Kim SY, Lee SH, Kim BM, Kim EH, Min BH, Bendayan M, et al. Activation of nestin-positive duct stem (NPDS) cells in pancreas upon neogenic motivation and possible cytodifferentiation into insulin-secreting cells from NPDS cells. Dev Dyn. 2004;230:1–11.CrossRefPubMed Kim SY, Lee SH, Kim BM, Kim EH, Min BH, Bendayan M, et al. Activation of nestin-positive duct stem (NPDS) cells in pancreas upon neogenic motivation and possible cytodifferentiation into insulin-secreting cells from NPDS cells. Dev Dyn. 2004;230:1–11.CrossRefPubMed
56.
Zurück zum Zitat May R, Sureban SM, Lightfoot SA, Hoskins AB, Brackett DJ, Postier RG, et al. Identification of a novel putative pancreatic stem/progenitor cell marker DCAMKL-1 in normal mouse pancreas. Am J Physiol Gastrointest Liver Physiol. 2010;299:G303–G10.CrossRefPubMedPubMedCentral May R, Sureban SM, Lightfoot SA, Hoskins AB, Brackett DJ, Postier RG, et al. Identification of a novel putative pancreatic stem/progenitor cell marker DCAMKL-1 in normal mouse pancreas. Am J Physiol Gastrointest Liver Physiol. 2010;299:G303–G10.CrossRefPubMedPubMedCentral
57.
Zurück zum Zitat Yamaguchi J, Liss AS, Sontheimer A, Mino-Kenudson M, Castillo CF, Warshaw AL, et al. Pancreatic duct glands (PDGs) are a progenitor compartment responsible for pancreatic ductal epithelial repair. Stem Cell Res. 2015;15:190–202.CrossRefPubMedPubMedCentral Yamaguchi J, Liss AS, Sontheimer A, Mino-Kenudson M, Castillo CF, Warshaw AL, et al. Pancreatic duct glands (PDGs) are a progenitor compartment responsible for pancreatic ductal epithelial repair. Stem Cell Res. 2015;15:190–202.CrossRefPubMedPubMedCentral
58.
Zurück zum Zitat Strobel O, Rosow DE, Rakhlin EY, Lauwers GY, Trainor AG, Alsina J, et al. Pancreatic duct glands are distinct ductal compartments that react to chronic injury and mediate Shh-induced metaplasia. Gastroenterology. 2010;138:1166–77.CrossRefPubMed Strobel O, Rosow DE, Rakhlin EY, Lauwers GY, Trainor AG, Alsina J, et al. Pancreatic duct glands are distinct ductal compartments that react to chronic injury and mediate Shh-induced metaplasia. Gastroenterology. 2010;138:1166–77.CrossRefPubMed
60.
Zurück zum Zitat Gopinathan A, Morton JP, Jodrell DI, Sansom OJ. GEMMs as preclinical models for testing pancreatic cancer therapies. Dis Model Mech. 2015;8:1185–200.CrossRefPubMedPubMedCentral Gopinathan A, Morton JP, Jodrell DI, Sansom OJ. GEMMs as preclinical models for testing pancreatic cancer therapies. Dis Model Mech. 2015;8:1185–200.CrossRefPubMedPubMedCentral
61.
Zurück zum Zitat Hingorani SR, Petricoin EF, Maitra A, Rajapakse V, King C, Jacobetz MA, et al. Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. Cancer Cell. 2003;4:437–50.CrossRefPubMed Hingorani SR, Petricoin EF, Maitra A, Rajapakse V, King C, Jacobetz MA, et al. Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. Cancer Cell. 2003;4:437–50.CrossRefPubMed
62.
Zurück zum Zitat Heinmoller E, Dietmaier W, Zirngibl H, Heinmoller P, Scaringe W, Jauch KW, et al. Molecular analysis of microdissected tumors and preneoplastic intraductal lesions in pancreatic carcinoma. Am J Pathol. 2000;157:83–92.CrossRefPubMedPubMedCentral Heinmoller E, Dietmaier W, Zirngibl H, Heinmoller P, Scaringe W, Jauch KW, et al. Molecular analysis of microdissected tumors and preneoplastic intraductal lesions in pancreatic carcinoma. Am J Pathol. 2000;157:83–92.CrossRefPubMedPubMedCentral
63.
Zurück zum Zitat Rozenblum E, Schutte M, Goggins M, Hahn SA, Panzer S, Zahurak M, et al. Tumor-suppressive pathways in pancreatic carcinoma. Cancer Res. 1997;57:1731–4.PubMed Rozenblum E, Schutte M, Goggins M, Hahn SA, Panzer S, Zahurak M, et al. Tumor-suppressive pathways in pancreatic carcinoma. Cancer Res. 1997;57:1731–4.PubMed
64.
Zurück zum Zitat Hingorani SR, Wang L, Multani AS, Combs C, Deramaudt TB, Hruban RH, et al. Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell. 2005;7:469–83.CrossRefPubMed Hingorani SR, Wang L, Multani AS, Combs C, Deramaudt TB, Hruban RH, et al. Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell. 2005;7:469–83.CrossRefPubMed
65.
Zurück zum Zitat Morton JP, Timpson P, Karim SA, Ridgway RA, Athineos D, Doyle B, et al. Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer. Proc Natl Acad Sci USA. 2010;107:246–51.CrossRefPubMed Morton JP, Timpson P, Karim SA, Ridgway RA, Athineos D, Doyle B, et al. Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer. Proc Natl Acad Sci USA. 2010;107:246–51.CrossRefPubMed
66.
Zurück zum Zitat Bardeesy N, Aguirre AJ, Chu GC, Cheng KH, Lopez LV, Hezel AF, et al. Both p16(Ink4a) and the p19(Arf)-p53 pathway constrain progression of pancreatic adenocarcinoma in the mouse. Proc Natl Acad Sci USA. 2006;103:5947–52.CrossRefPubMedPubMedCentral Bardeesy N, Aguirre AJ, Chu GC, Cheng KH, Lopez LV, Hezel AF, et al. Both p16(Ink4a) and the p19(Arf)-p53 pathway constrain progression of pancreatic adenocarcinoma in the mouse. Proc Natl Acad Sci USA. 2006;103:5947–52.CrossRefPubMedPubMedCentral
67.
Zurück zum Zitat Aguirre AJ, Bardeesy N, Sinha M, Lopez L, Tuveson DA, Horner J, et al. Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma. Genes Dev. 2003;17:3112–26.CrossRefPubMedPubMedCentral Aguirre AJ, Bardeesy N, Sinha M, Lopez L, Tuveson DA, Horner J, et al. Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma. Genes Dev. 2003;17:3112–26.CrossRefPubMedPubMedCentral
68.
Zurück zum Zitat Hill R, Calvopina JH, Kim C, Wang Y, Dawson DW, Donahue TR, et al. PTEN loss accelerates KrasG12D-induced pancreatic cancer development. Cancer Res. 2010;70:7114–24.CrossRefPubMedPubMedCentral Hill R, Calvopina JH, Kim C, Wang Y, Dawson DW, Donahue TR, et al. PTEN loss accelerates KrasG12D-induced pancreatic cancer development. Cancer Res. 2010;70:7114–24.CrossRefPubMedPubMedCentral
69.
Zurück zum Zitat Kennedy AL, Morton JP, Manoharan I, Nelson DM, Jamieson NB, Pawlikowski JS, et al. Activation of the PIK3CA/AKT pathway suppresses senescence induced by an activated RAS oncogene to promote tumorigenesis. Mol Cell. 2011;42:36–49.CrossRefPubMedPubMedCentral Kennedy AL, Morton JP, Manoharan I, Nelson DM, Jamieson NB, Pawlikowski JS, et al. Activation of the PIK3CA/AKT pathway suppresses senescence induced by an activated RAS oncogene to promote tumorigenesis. Mol Cell. 2011;42:36–49.CrossRefPubMedPubMedCentral
70.
Zurück zum Zitat Ijichi H, Chytil A, Gorska AE, Aakre ME, Fujitani Y, Fujitani S, et al. Aggressive pancreatic ductal adenocarcinoma in mice caused by pancreas-specific blockade of transforming growth factor-beta signaling in cooperation with active Kras expression. Genes Dev. 2006;20:3147–60.CrossRefPubMedPubMedCentral Ijichi H, Chytil A, Gorska AE, Aakre ME, Fujitani Y, Fujitani S, et al. Aggressive pancreatic ductal adenocarcinoma in mice caused by pancreas-specific blockade of transforming growth factor-beta signaling in cooperation with active Kras expression. Genes Dev. 2006;20:3147–60.CrossRefPubMedPubMedCentral
71.
Zurück zum Zitat Skoulidis F, Cassidy LD, Pisupati V, Jonasson JG, Bjarnason H, Eyfjord JE, et al. Germline Brca2 heterozygosity promotes Kras(G12D)-driven carcinogenesis in a murine model of familial pancreatic cancer. Cancer Cell. 2010;18:499–509.CrossRefPubMed Skoulidis F, Cassidy LD, Pisupati V, Jonasson JG, Bjarnason H, Eyfjord JE, et al. Germline Brca2 heterozygosity promotes Kras(G12D)-driven carcinogenesis in a murine model of familial pancreatic cancer. Cancer Cell. 2010;18:499–509.CrossRefPubMed
72.
Zurück zum Zitat Hanlon L, Avila JL, Demarest RM, Troutman S, Allen M, Ratti F, et al. Notch1 functions as a tumor suppressor in a model of K-ras-induced pancreatic ductal adenocarcinoma. Cancer Res. 2010;70:4280–6.CrossRefPubMedPubMedCentral Hanlon L, Avila JL, Demarest RM, Troutman S, Allen M, Ratti F, et al. Notch1 functions as a tumor suppressor in a model of K-ras-induced pancreatic ductal adenocarcinoma. Cancer Res. 2010;70:4280–6.CrossRefPubMedPubMedCentral
73.
Zurück zum Zitat Morton JP, Jamieson NB, Karim SA, Athineos D, Ridgway RA, Nixon C, et al. LKB1 haploinsufficiency cooperates with Kras to promote pancreatic cancer through suppression of p21-dependent growth arrest. Gastroenterology 2010;139:586–97, 97 e1–6CrossRefPubMedPubMedCentral Morton JP, Jamieson NB, Karim SA, Athineos D, Ridgway RA, Nixon C, et al. LKB1 haploinsufficiency cooperates with Kras to promote pancreatic cancer through suppression of p21-dependent growth arrest. Gastroenterology 2010;139:586–97, 97 e1–6CrossRefPubMedPubMedCentral
74.
Zurück zum Zitat Perez-Mancera PA, Rust AG, van der Weyden L, Kristiansen G, Li A, Sarver AL, et al. The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma. Nature. 2012;486:266–70.PubMedPubMedCentral Perez-Mancera PA, Rust AG, van der Weyden L, Kristiansen G, Li A, Sarver AL, et al. The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma. Nature. 2012;486:266–70.PubMedPubMedCentral
75.
Zurück zum Zitat Russell R, Perkhofer L, Liebau S, Lin Q, Lechel A, Feld FM, et al. Loss of ATM accelerates pancreatic cancer formation and epithelial-mesenchymal transition. Nat Commun. 2015;6:7677.CrossRefPubMedPubMedCentral Russell R, Perkhofer L, Liebau S, Lin Q, Lechel A, Feld FM, et al. Loss of ATM accelerates pancreatic cancer formation and epithelial-mesenchymal transition. Nat Commun. 2015;6:7677.CrossRefPubMedPubMedCentral
76.
Zurück zum Zitat Chalabi-Dchar M, Cassant-Sourdy S, Duluc C, Fanjul M, Lulka H, Samain R, et al. Loss of somatostatin receptor subtype 2 promotes growth of KRAS-induced pancreatic tumors in mice by activating PI3K signaling and overexpression of CXCL16. Gastroenterology. 2015;148:1452–65.CrossRefPubMed Chalabi-Dchar M, Cassant-Sourdy S, Duluc C, Fanjul M, Lulka H, Samain R, et al. Loss of somatostatin receptor subtype 2 promotes growth of KRAS-induced pancreatic tumors in mice by activating PI3K signaling and overexpression of CXCL16. Gastroenterology. 2015;148:1452–65.CrossRefPubMed
77.
Zurück zum Zitat Bardeesy N, Cheng KH, Berger JH, Chu GC, Pahler J, Olson P, et al. Smad4 is dispensable for normal pancreas development yet critical in progression and tumor biology of pancreas cancer. Genes Dev. 2006;20:3130–46.CrossRefPubMedPubMedCentral Bardeesy N, Cheng KH, Berger JH, Chu GC, Pahler J, Olson P, et al. Smad4 is dispensable for normal pancreas development yet critical in progression and tumor biology of pancreas cancer. Genes Dev. 2006;20:3130–46.CrossRefPubMedPubMedCentral
78.
Zurück zum Zitat Kojima K, Vickers SM, Adsay NV, Jhala NC, Kim HG, Schoeb TR, et al. Inactivation of Smad4 accelerates Kras(G12D)-mediated pancreatic neoplasia. Cancer Res. 2007;67:8121–30.CrossRefPubMed Kojima K, Vickers SM, Adsay NV, Jhala NC, Kim HG, Schoeb TR, et al. Inactivation of Smad4 accelerates Kras(G12D)-mediated pancreatic neoplasia. Cancer Res. 2007;67:8121–30.CrossRefPubMed
79.
Zurück zum Zitat Izeradjene K, Combs C, Best M, Gopinathan A, Wagner A, Grady WM, et al. Kras(G12D) and Smad4/Dpc4 haploinsufficiency cooperate to induce mucinous cystic neoplasms and invasive adenocarcinoma of the pancreas. Cancer Cell. 2007;11:229–43.CrossRefPubMed Izeradjene K, Combs C, Best M, Gopinathan A, Wagner A, Grady WM, et al. Kras(G12D) and Smad4/Dpc4 haploinsufficiency cooperate to induce mucinous cystic neoplasms and invasive adenocarcinoma of the pancreas. Cancer Cell. 2007;11:229–43.CrossRefPubMed
80.
Zurück zum Zitat Qiu W, Tang SM, Lee S, Turk AT, Sireci AN, Qiu A, et al. Loss of activin receptor type 1B accelerates development of intraductal papillary mucinous neoplasms in mice with activated KRAS. Gastroenterology 2016;150:218 e12–228 e12.CrossRef Qiu W, Tang SM, Lee S, Turk AT, Sireci AN, Qiu A, et al. Loss of activin receptor type 1B accelerates development of intraductal papillary mucinous neoplasms in mice with activated KRAS. Gastroenterology 2016;150:218 e12–228 e12.CrossRef
81.
Zurück zum Zitat Yamaguchi J, Mino-Kenudson M, Liss AS, Chowdhury S, Wang TC, Castillo CF, et al. Loss of trefoil factor 2 From pancreatic duct glands promotes formation of intraductal papillary mucinous neoplasms in mice. Gastroenterology 2016. Yamaguchi J, Mino-Kenudson M, Liss AS, Chowdhury S, Wang TC, Castillo CF, et al. Loss of trefoil factor 2 From pancreatic duct glands promotes formation of intraductal papillary mucinous neoplasms in mice. Gastroenterology 2016.
82.
Zurück zum Zitat Siveke JT, Einwachter H, Sipos B, Lubeseder-Martellato C, Kloppel G, Schmid RM. Concomitant pancreatic activation of Kras(G12D) and Tgfa results in cystic papillary neoplasms reminiscent of human IPMN. Cancer Cell. 2007;12:266–79.CrossRefPubMed Siveke JT, Einwachter H, Sipos B, Lubeseder-Martellato C, Kloppel G, Schmid RM. Concomitant pancreatic activation of Kras(G12D) and Tgfa results in cystic papillary neoplasms reminiscent of human IPMN. Cancer Cell. 2007;12:266–79.CrossRefPubMed
83.
Zurück zum Zitat Sano M, Driscoll DR, De Jesus-Monge WE, Klimstra DS, Lewis BC. Activated wnt signaling in stroma contributes to development of pancreatic mucinous cystic neoplasms. Gastroenterology. 2014;146:257–67.CrossRefPubMed Sano M, Driscoll DR, De Jesus-Monge WE, Klimstra DS, Lewis BC. Activated wnt signaling in stroma contributes to development of pancreatic mucinous cystic neoplasms. Gastroenterology. 2014;146:257–67.CrossRefPubMed
84.
Zurück zum Zitat Mazur PK, Einwachter H, Lee M, Sipos B, Nakhai H, Rad R, et al. Notch2 is required for progression of pancreatic intraepithelial neoplasia and development of pancreatic ductal adenocarcinoma. Proc Natl Acad Sci USA. 2010;107:13438–43.CrossRefPubMedPubMedCentral Mazur PK, Einwachter H, Lee M, Sipos B, Nakhai H, Rad R, et al. Notch2 is required for progression of pancreatic intraepithelial neoplasia and development of pancreatic ductal adenocarcinoma. Proc Natl Acad Sci USA. 2010;107:13438–43.CrossRefPubMedPubMedCentral
85.
Zurück zum Zitat Vincent DF, Yan KP, Treilleux I, Gay F, Arfi V, Kaniewski B, et al. Inactivation of TIF1gamma cooperates with Kras to induce cystic tumors of the pancreas. PLoS Genet. 2009;5:e1000575.CrossRefPubMedPubMedCentral Vincent DF, Yan KP, Treilleux I, Gay F, Arfi V, Kaniewski B, et al. Inactivation of TIF1gamma cooperates with Kras to induce cystic tumors of the pancreas. PLoS Genet. 2009;5:e1000575.CrossRefPubMedPubMedCentral
86.
Zurück zum Zitat De La OJ, Emerson LL, Goodman JL, Froebe SC, Illum BE, Curtis AB, et al. Notch and Kras reprogram pancreatic acinar cells to ductal intraepithelial neoplasia. Proc Natl Acad Sci USA. 2008;105:18907–12.CrossRef De La OJ, Emerson LL, Goodman JL, Froebe SC, Illum BE, Curtis AB, et al. Notch and Kras reprogram pancreatic acinar cells to ductal intraepithelial neoplasia. Proc Natl Acad Sci USA. 2008;105:18907–12.CrossRef
87.
Zurück zum Zitat Shi G, Zhu L, Sun Y, Bettencourt R, Damsz B, Hruban RH, et al. Loss of the acinar-restricted transcription factor Mist1 accelerates Kras-induced pancreatic intraepithelial neoplasia. Gastroenterology. 2009;136:1368–78.CrossRefPubMedPubMedCentral Shi G, Zhu L, Sun Y, Bettencourt R, Damsz B, Hruban RH, et al. Loss of the acinar-restricted transcription factor Mist1 accelerates Kras-induced pancreatic intraepithelial neoplasia. Gastroenterology. 2009;136:1368–78.CrossRefPubMedPubMedCentral
88.
Zurück zum Zitat Brembeck FH, Schreiber FS, Deramaudt TB, Craig L, Rhoades B, Swain G, et al. The mutant K-ras oncogene causes pancreatic periductal lymphocytic infiltration and gastric mucous neck cell hyperplasia in transgenic mice. Cancer Res. 2003;63:2005–9.PubMed Brembeck FH, Schreiber FS, Deramaudt TB, Craig L, Rhoades B, Swain G, et al. The mutant K-ras oncogene causes pancreatic periductal lymphocytic infiltration and gastric mucous neck cell hyperplasia in transgenic mice. Cancer Res. 2003;63:2005–9.PubMed
89.
Zurück zum Zitat Ray KC, Bell KM, Yan J, Gu G, Chung CH, Washington MK, et al. Epithelial tissues have varying degrees of susceptibility to Kras(G12D)-initiated tumorigenesis in a mouse model. PLoS One. 2011;6:e16786.CrossRefPubMedPubMedCentral Ray KC, Bell KM, Yan J, Gu G, Chung CH, Washington MK, et al. Epithelial tissues have varying degrees of susceptibility to Kras(G12D)-initiated tumorigenesis in a mouse model. PLoS One. 2011;6:e16786.CrossRefPubMedPubMedCentral
90.
Zurück zum Zitat von Figura G, Morris JPt, Wright CV, Hebrok M. Nr5a2 maintains acinar cell differentiation and constrains oncogenic Kras-mediated pancreatic neoplastic initiation. Gut. 2014;63:656–64.CrossRef von Figura G, Morris JPt, Wright CV, Hebrok M. Nr5a2 maintains acinar cell differentiation and constrains oncogenic Kras-mediated pancreatic neoplastic initiation. Gut. 2014;63:656–64.CrossRef
91.
Zurück zum Zitat Roy N, Malik S, Villanueva KE, Urano A, Lu X, Von Figura G, et al. Brg1 promotes both tumor-suppressive and oncogenic activities at distinct stages of pancreatic cancer formation. Genes Dev. 2015;29:658–71.CrossRefPubMedPubMedCentral Roy N, Malik S, Villanueva KE, Urano A, Lu X, Von Figura G, et al. Brg1 promotes both tumor-suppressive and oncogenic activities at distinct stages of pancreatic cancer formation. Genes Dev. 2015;29:658–71.CrossRefPubMedPubMedCentral
92.
Zurück zum Zitat von Figura G, Fukuda A, Roy N, Liku ME, Morris Iv JP, Kim GE, et al. The chromatin regulator Brg1 suppresses formation of intraductal papillary mucinous neoplasm and pancreatic ductal adenocarcinoma. Nat Cell Biol. 2014;16:255–67.CrossRef von Figura G, Fukuda A, Roy N, Liku ME, Morris Iv JP, Kim GE, et al. The chromatin regulator Brg1 suppresses formation of intraductal papillary mucinous neoplasm and pancreatic ductal adenocarcinoma. Nat Cell Biol. 2014;16:255–67.CrossRef
93.
Zurück zum Zitat Reichert M, Blume K, Kleger A, Hartmann D, von Figura G. Developmental pathways direct pancreatic cancer initiation from its cellular origin. Stem Cells Int. 2016;2016:9298535.CrossRefPubMed Reichert M, Blume K, Kleger A, Hartmann D, von Figura G. Developmental pathways direct pancreatic cancer initiation from its cellular origin. Stem Cells Int. 2016;2016:9298535.CrossRefPubMed
95.
Zurück zum Zitat Ji B, Tsou L, Wang H, Gaiser S, Chang DZ, Daniluk J, et al. Ras activity levels control the development of pancreatic diseases. Gastroenterology 2009;137:1072–82, 82 e1–6.CrossRefPubMedPubMedCentral Ji B, Tsou L, Wang H, Gaiser S, Chang DZ, Daniluk J, et al. Ras activity levels control the development of pancreatic diseases. Gastroenterology 2009;137:1072–82, 82 e1–6.CrossRefPubMedPubMedCentral
96.
Zurück zum Zitat Bailey JM, Hendley AM, Lafaro KJ, Pruski MA, Jones NC, Alsina J, et al. p53 mutations cooperate with oncogenic Kras to promote adenocarcinoma from pancreatic ductal cells. Oncogene. 2016;35:4282–8.CrossRefPubMed Bailey JM, Hendley AM, Lafaro KJ, Pruski MA, Jones NC, Alsina J, et al. p53 mutations cooperate with oncogenic Kras to promote adenocarcinoma from pancreatic ductal cells. Oncogene. 2016;35:4282–8.CrossRefPubMed
97.
Zurück zum Zitat Gidekel Friedlander SY, Chu GC, Snyder EL, Girnius N, Dibelius G, Crowley D, et al. Context-dependent transformation of adult pancreatic cells by oncogenic K-Ras. Cancer Cell. 2009;16:379–89.CrossRefPubMedPubMedCentral Gidekel Friedlander SY, Chu GC, Snyder EL, Girnius N, Dibelius G, Crowley D, et al. Context-dependent transformation of adult pancreatic cells by oncogenic K-Ras. Cancer Cell. 2009;16:379–89.CrossRefPubMedPubMedCentral
98.
Zurück zum Zitat Guerra C, Collado M, Navas C, Schuhmacher AJ, Hernandez-Porras I, Canamero M, et al. Pancreatitis-induced inflammation contributes to pancreatic cancer by inhibiting oncogene-induced senescence. Cancer Cell. 2011;19:728–39.CrossRefPubMedPubMedCentral Guerra C, Collado M, Navas C, Schuhmacher AJ, Hernandez-Porras I, Canamero M, et al. Pancreatitis-induced inflammation contributes to pancreatic cancer by inhibiting oncogene-induced senescence. Cancer Cell. 2011;19:728–39.CrossRefPubMedPubMedCentral
99.
Zurück zum Zitat Stanger BZ, Stiles B, Lauwers GY, Bardeesy N, Mendoza M, Wang Y, et al. Pten constrains centroacinar cell expansion and malignant transformation in the pancreas. Cancer Cell. 2005;8:185–95.CrossRefPubMed Stanger BZ, Stiles B, Lauwers GY, Bardeesy N, Mendoza M, Wang Y, et al. Pten constrains centroacinar cell expansion and malignant transformation in the pancreas. Cancer Cell. 2005;8:185–95.CrossRefPubMed
100.
Zurück zum Zitat Carriere C, Seeley ES, Goetze T, Longnecker DS, Korc M. The Nestin progenitor lineage is the compartment of origin for pancreatic intraepithelial neoplasia. Proc Natl Acad Sci USA. 2007;104:4437–42.CrossRefPubMedPubMedCentral Carriere C, Seeley ES, Goetze T, Longnecker DS, Korc M. The Nestin progenitor lineage is the compartment of origin for pancreatic intraepithelial neoplasia. Proc Natl Acad Sci USA. 2007;104:4437–42.CrossRefPubMedPubMedCentral
101.
Zurück zum Zitat Delgiorno KE, Hall JC, Takeuchi KK, Pan FC, Halbrook CJ, Washington MK, et al. Identification and manipulation of biliary metaplasia in pancreatic tumors. Gastroenterology 2014;146:233–44 e5. Delgiorno KE, Hall JC, Takeuchi KK, Pan FC, Halbrook CJ, Washington MK, et al. Identification and manipulation of biliary metaplasia in pancreatic tumors. Gastroenterology 2014;146:233–44 e5.
102.
Zurück zum Zitat Bailey JM, Alsina J, Rasheed ZA, McAllister FM, Fu YY, Plentz R, et al. DCLK1 marks a morphologically distinct subpopulation of cells with stem cell properties in preinvasive pancreatic cancer. Gastroenterology. 2014;146:245–56.CrossRefPubMed Bailey JM, Alsina J, Rasheed ZA, McAllister FM, Fu YY, Plentz R, et al. DCLK1 marks a morphologically distinct subpopulation of cells with stem cell properties in preinvasive pancreatic cancer. Gastroenterology. 2014;146:245–56.CrossRefPubMed
Metadaten
Titel
Cells of origin of pancreatic neoplasms
verfasst von
Junpei Yamaguchi
Yukihiro Yokoyama
Toshio Kokuryo
Tomoki Ebata
Masato Nagino
Publikationsdatum
04.03.2017
Verlag
Springer Japan
Erschienen in
Surgery Today / Ausgabe 1/2018
Print ISSN: 0941-1291
Elektronische ISSN: 1436-2813
DOI
https://doi.org/10.1007/s00595-017-1501-2

Weitere Artikel der Ausgabe 1/2018

Surgery Today 1/2018 Zur Ausgabe

Leitlinien kompakt für die Allgemeinmedizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Facharzt-Training Allgemeinmedizin

Die ideale Vorbereitung zur anstehenden Prüfung mit den ersten 24 von 100 klinischen Fallbeispielen verschiedener Themenfelder

Mehr erfahren

Update Allgemeinmedizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.