Pancreatic duct-like cell line derived from pig embryonic stem cells: expression of uroplakin genes in pig pancreatic tissue

Abstract

The isolation of a cell line, PICM-31D, with phenotypic characteristics like pancreatic duct cells is described. The PICM-31D cell line was derived from the previously described pig embryonic stem cell-derived exocrine pancreatic cell line, PICM-31. The PICM-31D cell line was morphologically distinct from the parental cells in growing as a monolayer rather than self-assembling into multicellular acinar-like structures. The PICM-31D cells were propagated for over a year at split ratios of 1:3 to 1:10 at each passage without change in phenotype or growth rate. Electron microscopy showed the cells to be a polarized epithelium of cuboidal cells joined by tight junction-like adhesions at their apical/lateral aspect. The cells contained numerous mucus-like secretory vesicles under their apical cell membrane. Proteomic analysis of the PICM-31D’s cellular proteins detected MUC1 and MUC4, consistent with mucus vesicle morphology. Gene expression analysis showed the cells expressed pancreatic ductal cell-related transcription factors such as GATA4, GATA6, HES1, HNF1A, HNF1B, ONECUT1 (HNF6), PDX1, and SOX9, but little or no pancreas progenitor cell markers such as PTF1A, NKX6-1, SOX2, or NGN3. Pancreas ductal cell-associated genes including CA2, CFTR, MUC1, MUC5B, MUC13, SHH, TFF1, KRT8, and KRT19 were expressed by the PICM-31D cells, but the exocrine pancreas marker genes, CPA1 and PLA2G1B, were not expressed by the cells. However, the exocrine marker, AMY2A, was still expressed by the cells. Surprisingly, uroplakin proteins were prominent in the PICM-31D cell proteome, particularly UPK1A. Annexin A1 and A2 proteins were also relatively abundant in the cells. The expression of the uroplakin and annexin genes was detected in the cells, although only UPK1B, UPK3B, ANXA2, and ANXA4 were detected in fetal pig pancreatic duct tissue. In conclusion, the PICM-31D cell line models the mucus-secreting ductal cells of the fetal pig pancreas.

This is a preview of subscription content, access via your institution.

Figure 1.
Figure 2.
Figure 3.
Figure 4.
Figure 5.
Figure 6.

References

  1. Allen A, Hutton DA, Pearson JP (1998) The MUC2 gene product: a human intestinal mucin. Int J Biochem Cell Biol 30:797–801

    Article  CAS  PubMed  Google Scholar 

  2. Amsterdam A, Raanan C, Schreiber L, Polin N, Givol D (2013) LGR5 and Nanog identify stem cell signature of pancreas beta cells which initiate pancreatic cancer. Biochem Biophys Res Commun 433:157–162

    Article  CAS  PubMed  Google Scholar 

  3. Andrianifahanana M, Moniaux N, Schmied BM, Ringel J, Friess H, Hollingsworth MA, Büchler MW, Aubert JP, Batra SK (2001) Mucin (MUC) gene expression in human pancreatic adenocarcinoma and chronic pancreatitis: a potential role of MUC4 as a tumor marker of diagnostic significance. Clin Cancer Res 7:4033–4040

    CAS  PubMed  Google Scholar 

  4. Augeron C, Laboisse CL (1984) Emergence of permanently differentiated cell clones in a human colonic cancer cell line in culture after treatment with sodium butyrate. Cancer Res 44:3961–3969

    CAS  PubMed  Google Scholar 

  5. Bai XF, Ni XG, Zhao P, Liu SM, Wang HX, Guo B, Zhou LP, Liu F, Zhang JS, Wang K, Xie YQ, Shao YF, Zhao XH (2004) Overexpression of annexin 1 in pancreatic cancer and its clinical significance. World J Gastroenterol 10:1466–1470

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Balagué C, Audié JP, Porchet N, Real FX (1995) In situ hybridization shows distinct patterns of mucin gene expression in normal, benign, and malignant pancreas tissues. Gastroenterology. 109:953–964

    Article  PubMed  Google Scholar 

  7. Berberat PO, Friess H, Wang L, Zhu Z, Bley T, Frigeri L, Zimmermann A, Büchler MW (2001) Comparative analysis of galectins in primary tumors and tumor metastasis in human pancreatic cancer. J Histochem Cytochem 49:539–549

    Article  CAS  PubMed  Google Scholar 

  8. Besnard V, Wert SE, Hull WM, Whitsett JA (2004) Immunohistochemical localization of Foxa1 and Foxa2 in mouse embryos and adult tissues. Gene Expr Patterns 5:193–208

    Article  CAS  PubMed  Google Scholar 

  9. Buisine MP, Devisme L, Degand P, Dieu MC, Gosselin B, Copin MC, Aubert JP, Porchet N (2000) Developmental mucin gene expression in the gastroduodenal tract and accessory digestive glands. II. Duodenum and liver, gallbladder, and pancreas. J Histochem Cytochem 48:1667–1676

    Article  CAS  PubMed  Google Scholar 

  10. Cano DA, Soria B, Martín F, Rojas A (2014) Transcriptional control of mammalian pancreas organogenesis. Cell Mol Life Sci 71:2383–2402

    Article  CAS  PubMed  Google Scholar 

  11. Chaturvedi P, Singh AP, Moniaux N, Senapati S, Chakraborty S, Meza JL, Batra SK (2007) MUC4 mucin potentiates pancreatic tumor cell proliferation survival and invasive properties and interferes with its interaction to extracellular matrix proteins. Mol Cancer Res 5:309–320

    Article  CAS  PubMed  Google Scholar 

  12. Cheng JY, Whitelock J, Poole-Warren L (2012) Syndecan-4 is associated with beta-cells in the pancreas and the MIN6 beta-cell line. Histochem Cell Biol 138:933–944

    Article  CAS  PubMed  Google Scholar 

  13. Choi JH, Lee MY, Kim Y, Shim JY, Han SM, Lee KA, Choi YK, Jeon HM, Baek KH (2010) Isolation of genes involved in pancreas regeneration by subtractive hybridization. Biol Chem 391:1019–1029

    Article  CAS  PubMed  Google Scholar 

  14. Christophe J (1994) Pancreatic tumoral cell line AR42J: an amphicrine model. Am J Phys 266:G963–G971

    CAS  Google Scholar 

  15. Conejo JR, Kleeff J, Koliopanos A, Matsuda K, Zhu ZW, Goecke H, Bicheng N, Zimmermann A, Korc M, Friess H, Büchler MW (2000) Syndecan-1 expression is up-regulated in pancreatic but not in other gastrointestinal cancers. Int J Cancer 88:12–20

    Article  CAS  PubMed  Google Scholar 

  16. Deer EL, González-Hernández J, Coursen JD, Shea JE, Ngatia J, Scaife CL, Firpo MA, Mulvihill SJ (2010) Phenotype and genotype of pancreatic cancer cell lines. Pancreas. 39:425–435

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Egerbacher M, Böck P (1997) Morphology of the pancreatic duct system in mammals. Microsc Res Tech 37:407–417

    Article  CAS  PubMed  Google Scholar 

  18. Foulon T, Cadel S, Chesneau V, Draoui M, Prat A, Cohen P (1996) Two novel metallopeptidases with a specificity for basic residues: functional properties, structure and cellular distribution. Ann N Y Acad Sci 780:106–120

    Article  CAS  PubMed  Google Scholar 

  19. Furukawa T, Duguid WP, Rosenberg L, Viallet J, Galloway DA, Tsao MS (1996) Long-term culture and immortalization of epithelial cells from normal adult human pancreatic ducts transfected by the E6E7 gene of human papilloma virus 16. Am J Pathol 148:1763–1770

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Gaisano HY, Ghai M, Malkus PN, Sheu L, Bouquillon A, Bennett MK, Trimble WS (1996) Distinct cellular locations of the syntaxin family of proteins in rat pancreatic acinar cells. Mol Biol Cell 7:2019–2027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gautam SK, Kumar S, Cannon A, Hall B, Bhatia R, Nasser MW, Mahapatra S, Batra SK, Jain M (2017) MUC4 mucin—a therapeutic target for pancreatic ductal adenocarcinoma. Expert Opin Ther Targets 21:657–669

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Githens S (1988) The pancreatic duct cell: proliferative capabilities, specific characteristics, metaplasia, isolation, and culture. Pediatr Gastroenterol Nutr 7:486–506

    Article  CAS  Google Scholar 

  23. Githens S, Schexnayder JA, Frazier ML (1992) Carbonic anhydrase II gene expression in mouse pancreatic duct cells. Pancreas. 7:556–561

  24. Githens S, Schexnayder JA, Moses RL, Denning GM, Smith JJ, Frazier ML (1994) Mouse pancreatic acinar/ductular tissue gives rise to epithelial cultures that are morphologically, biochemically, and functionally indistinguishable from interlobular duct cell cultures. In Vitro Cell Dev Biol Anim 30A:622–635

  25. Githens S 3rd, Holmquist DR, Whelan JF, Ruby JR (1981) Morphologic and biochemical characteristics of isolated and cultured pancreatic ducts. Cancer. 47:1505–1512

  26. Gittes GK (2009) Developmental biology of the pancreas: a comprehensive review. Dev Biol 326:4–35

    Article  CAS  PubMed  Google Scholar 

  27. Gomez DL, O’Driscoll M, Sheets TP, Hruban RH, Oberholzer J, McGarrigle JJ, Shamblott MJ (2015) Neurogenin 3 expressing cells in the human exocrine pancreas have the capacity for endocrine cell fate. PLoS One 10(8):e0133862. https://doi.org/10.1371/journal.pone.0133862

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Grapin-Botton A (2005) Ductal cells of the pancreas. Int J Biochem Cell Biol 37:504–510

    Article  CAS  PubMed  Google Scholar 

  29. Grønborg M, Kristiansen TZ, Iwahori A, Chang R, Reddy R, Sato N, Molina H, Jensen ON, Hruban RH, Goggins MG, Maitra A, Pandey A (2006) Biomarker discovery from pancreatic cancer secretome using a differential proteomic approach. Mol Cell Proteomics 5:157–171

    Article  CAS  PubMed  Google Scholar 

  30. Gu G, Dubauskaite J, Melton DA (2002) Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and are distinct from duct progenitors. Development 129:2447–2457

    CAS  PubMed  Google Scholar 

  31. Harris A, Coleman L (1987) Establishment of a tissue culture system for epithelial cells derived from human pancreas: a model for the study of cystic fibrosis. J Cell Sci 87:695–703

    PubMed  Google Scholar 

  32. Hausmann DH, Porstmann T, Weber I, Hausmann S, Dummler W, Liebe S, Emmrich J (1997) Cu/Zn-SOD in human pancreatic tissue and pancreatic juice. Int J Pancreatol 22:207–213

    CAS  PubMed  Google Scholar 

  33. He L, Diedrich J, Chu YY, Yates JR 3rd (2015a) Extracting accurate precursor information for tandem mass spectra by RawConverter. Anal Chem 87:11361–11367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. He P, Jiang S, Ma M, Wang Y, Li R, Fang F, Tian G, Zhang Z (2015b) Trophoblast glycoprotein promotes pancreatic ductal adenocarcinoma cell metastasis through Wnt/planar cell polarity signaling. Mol Med Rep 12:503–509

    Article  CAS  PubMed  Google Scholar 

  35. Hebrok M, Kim SK, St Jacques B, McMahon AP, Melton DA (2000) Regulation of pancreas development by hedgehog signaling. Development 127:4905–4913

    CAS  PubMed  Google Scholar 

  36. Heller RS, Dichmann DS, Jensen J, Miller C, Wong G, Madsen OD, Serup P (2002) Expression patterns of Wnts, Frizzleds, sFRPs, and misexpression in transgenic mice suggesting a role for Wnts in pancreas and foregut pattern formation. Dev Dyn 225:260–270

    Article  CAS  PubMed  Google Scholar 

  37. Iio T, Tamaoki T (1976) Intracellular distribution of alpha-fetoprotein and albumin messenger RNAs in developing mouse liver. Can J Biochem 54:408–412

    Article  CAS  PubMed  Google Scholar 

  38. Jensen J (2004) Gene regulatory factors in pancreatic development. Dev Dyn 229:176–200

    Article  CAS  PubMed  Google Scholar 

  39. Jiang FX, Naselli G, Harrison LC (2002) Distinct distribution of laminin and its integrin receptors in the pancreas. J Histochem Cytochem 50:1625–1632

    Article  CAS  PubMed  Google Scholar 

  40. Jones EA, Clement-Jones M, James OF, Wilson DI (2001) Differences between human and mouse alpha-fetoprotein expression during early development. J Anat 198:555–559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Karanjawala ZE, Illei PB, Ashfaq R, Infante JR, Murphy K, Pandey A, Schulick R, Winter J, Sharma R, Maitra A, Goggins M, Hruban RH (2008) New markers of pancreatic cancer identified through differential gene expression analyses: claudin 18 and annexin A8. Am J Surg Pathol 32:188–196

    Article  PubMed  PubMed Central  Google Scholar 

  42. Kawaguchi Y, Cooper B, Gannon M, Ray M, MacDonald RJ, Wright CV (2002) The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors. Nat Genet 32:128–134

    Article  CAS  PubMed  Google Scholar 

  43. Keller A, Nesvizhskii AI, Kolker E, Aebersold R (2002) Empirical statistical model to estimate the accuracy of peptide identificationsm made by MS/MS and database search. Anal Chem 74:5383–5392

    Article  CAS  PubMed  Google Scholar 

  44. Khushman M, Bhardwaj A, Patel GK, Laurini JA, Roveda K, Tan MC, Patton MC, Singh S, Taylor W, Singh AP (2017) Exosomal markers (CD63 and CD9) expression pattern using immunohistochemistry in resected malignant and nonmalignant pancreatic specimens. Pancreas. 46:782–788

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Kim BM, Han YM, Shin YJ, Min BH, Park IS (2001) Clusterin expression during regeneration of pancreatic islet cells in streptozotocin-induced diabetic rats. Diabetologia. 44:2192–2202

    Article  CAS  PubMed  Google Scholar 

  46. Kobayashi E, Hishikawa S, Teratani T, Lefor AT (2012) The pig as a model for translational research: overview of porcine animal models at Jichi Medical University. Transplant Res 1:8

    Article  PubMed  PubMed Central  Google Scholar 

  47. Kolar C, Caffrey T, Hollingsworth M, Scheetz M, Sutherlin M, Weide L, Lawson T (1997) Duct epithelial cells cultured from human pancreas processed for transplantation retain differentiated ductal characteristics. Pancreas. 15:265–271

    Article  CAS  PubMed  Google Scholar 

  48. Kopinke D, Brailsford M, Shea JE, Leavitt R, Scaife CL, Murtaugh LC (2011) Lineage tracing reveals the dynamic contribution of Hes1+ cells to the developing and adult pancreas. Development 138:431–441

  49. Kopinke D, Murtaugh LC (2010) Exocrine-to-endocrine differentiation is detectable only prior to birth in the uninjured mouse pancreas. BMC Dev Biol 10:38

  50. Kuo KK, Kuo CJ, Chiu CY, Liang SS, Huang CH, Chi SW, Tsai KB, Chen CY, Hsi E, Cheng KH, Chiou SH (2016) Quantitative proteomic analysis of differentially expressed protein profiles involved in pancreatic ductal adenocarcinoma. Pancreas 45:71–83

  51. Kuo WL, Montag AG, Rosner MR (1993) Insulin-degrading enzyme is differentially expressed and developmentally regulated in various rat tissues. Endocrinology 132:604–611

  52. Larsen HL, Grapin-Botton A (2017) The molecular and morphogenetic basis of pancreas organogenesis. Semin Cell Dev Biol 66:51–68

    Article  CAS  PubMed  Google Scholar 

  53. Lee G (2011) Uroplakins in the lower urinary tract. Int Neurourol J 15:4–12

    Article  PubMed  PubMed Central  Google Scholar 

  54. Lee KM, Nguyen C, Ulrich AB, Pour PM, Ouellette MM (2003) Immortalization with telomerase of the Nestin-positive cells of the human pancreas. Biochem Biophys Res Commun 301:1038–1044

    Article  CAS  PubMed  Google Scholar 

  55. Lee S, Hong SW, Min BH, Shim YJ, Lee KU, Lee IK, Bendayan M, Aronow BJ, Park IS (2011) Essential role of clusterin in pancreas regeneration. Dev Dyn 240:605–615

    Article  CAS  PubMed  Google Scholar 

  56. Lesuffleur T, Barbat A, Dussaulx E, Zweibaum A (1990) Growth adaptation to methotrexate of HT-29 human colon carcinoma cells is associated with their ability to differentiate into columnar absorptive and mucus-secreting cells. Cancer Res 50:6334–6343

    CAS  PubMed  Google Scholar 

  57. Li WC, Rukstalis JM, Nishimura W, Tchipashvili V, Habener JF, Sharma A, Bonner-Weir S (2010) Activation of pancreatic-duct-derived progenitor cells during pancreas regeneration in adult rats. J Cell Sci 123:2792–2802

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Liu N, Furukawa T, Kobari M, Tsao MS (1998) Comparative phenotypic studies of duct epithelial cell lines derived from normal human pancreas and pancreatic carcinoma. Am J Pathol 153:263–269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Lowe AW, Olsen M, Hao Y, Lee SP, Taek Lee K, Chen X, van de Rijn M, Brown PO (2007) Gene expression patterns in pancreatic tumors, cells and tissues. PLoS One 2(3):e323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Lukinius A, Stridsberg M, Wilander E (2003) Cellular expression and specific intragranular localization of chromogranin A, chromogranin B, and synaptophysin during ontogeny of pancreatic islet cells: an ultrastructural study. Pancreas 27:38–46

    Article  CAS  PubMed  Google Scholar 

  61. Lundgren DH, Hwang SI, Wu L, Han DK (2010) Role of spectral counting in quantitative proteomics. Expert Rev Proteomics 7:39–53

    Article  CAS  PubMed  Google Scholar 

  62. Madden ME, Sarras MP Jr (1988) Morphological and biochemical characterization of a human pancreatic ductal cell line (PANC-1). Pancreas 3:512–528

    Article  CAS  PubMed  Google Scholar 

  63. Marino LR, Cotton CU (1996) Immortalization of bovine pancreatic duct epithelial cells. Am J Phys 270:G676–G683

    CAS  Google Scholar 

  64. Marshall BA, Tordjman K, Host HH, Ensor NJ, Kwon G, Marshall CA, Coleman T, McDaniel ML, Semenkovich CF (1999) Relative hypoglycemia and hyperinsulinemia in mice with heterozygous lipoprotein lipase (LPL) deficiency. Islet LPL regulates insulin secretion. J Biol Chem 274:27426–27432

    Article  CAS  PubMed  Google Scholar 

  65. Maurer M, Müller AC, Parapatics K, Pickl WF, Wagner C, Rudashevskaya EL, Breitwieser FP, Colinge J, Garg K, Griss J, Bennett KL, Wagner SN (2014) Comprehensive comparative and semiquantitative proteome of a very low number of native and matched Epstein-Barr-virus-transformed B lymphocytes infiltrating human melanoma. J Proteome Res 13:2830–2845

    Article  CAS  PubMed  Google Scholar 

  66. Nesvizhskii AI, Keller A, Kolker E, Aebersold R (2003) A statistical model for identifying proteins by tandem mass spectrometry. Anal Chem 75:4646–4658

    Article  CAS  Google Scholar 

  67. Nishide T, Emi M, Nakamura Y, Matsubara K (1984) Corrected sequences of cDNAs for human salivary and pancreatic alpha-amylases [corrected]. Gene. 28:263–270

    Article  CAS  PubMed  Google Scholar 

  68. Nishii Y, Yamaguchi M, Kimura Y, Hasegawa T, Aburatani H, Uchida H, Hirata K, Sakuma Y (2015) A newly developed anti-mucin 13 monoclonal antibody targets pancreatic ductal adenocarcinoma cells. Int J Oncol 46:1781–1787

    Article  CAS  PubMed  Google Scholar 

  69. Oda D, Savard CE, Nguyen TD, Eng L, Swenson ER, Lee SP (1996) Dog pancreatic duct epithelial cells: long-term culture and characterization. Am J Pathol 148:977–985

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Ohta T, Terada T, Nagakawa T, Itoh H, Tajima H, Miyazaki I (1994) Presence of pancreatic alpha-amylase, trypsinogen, and lipase immunoreactivity in normal human pancreatic ducts. Pancreas 9:382–386

    Article  CAS  PubMed  Google Scholar 

  71. Ouyang H, Mou LJ, Luk C, Liu N, Karaskova J, Squire J, Tsao MS (2000) Immortal human pancreatic duct epithelial cell lines with near normal genotype and phenotype. Am J Pathol 157:1623–1631

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Pacifici F, Arriga R, Sorice GP, Capuani B, Scioli MG, Pastore D, Donadel G, Bellia A, Caratelli S, Coppola A, Ferrelli F, Federici M, Sconocchia G, Tesauro M, Sbraccia P, Della-Morte D, Giaccari A, Orlandi A, Lauro D (2014) Peroxiredoxin 6, a novel player in the pathogenesis of diabetes. Diabetes. 63:3210–3220

    Article  CAS  PubMed  Google Scholar 

  73. Pallagi P, Hegyi P, Rakonczay Z Jr (2015) The physiology and pathophysiology of pancreatic ductal secretion: the background for clinicians. Pancreas. 44:1211–1233

    Article  CAS  PubMed  Google Scholar 

  74. Rausa F, Samadani U, Ye H, Lim L, Fletcher CF, Jenkins NA, Copeland NG, Costa RH (1997) The cut-homeodomain transcriptional activator HNF-6 is coexpressed with its target gene HNF-3 beta in the developing murine liver and pancreas. Dev Biol 192:228–246

    Article  CAS  PubMed  Google Scholar 

  75. Reichert M, Rustgi AK (2011) Pancreatic ductal cells in development, regeneration, and neoplasia. J Clin Invest 121:4572–4578

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Rezanejad H, Ouziel-Yahalom L, Keyzer CA, Sullivan BA, Hollister-Lock J, Li WC, Guo L, Deng S, Lei J, Markmann J, Bonner-Weir S (2018) Heterogeneity of SOX9 and HNF1β in pancreatic ducts is dynamic. Stem Cell Rep 10:725–738

    Article  CAS  Google Scholar 

  77. Schaffer AE, Taylor BL, Benthuysen JR, Liu J, Thorel F, Yuan W, Jiao Y, Kaestner KH, Herrera PL, Magnuson MA, May CL, Sander M (2013) Nkx6.1 controls a gene regulatory network required for establishing and maintaining pancreatic beta cell identity. PLoS Genet 9:e1003274. https://doi.org/10.1371/journal.pgen.1003274

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Seyama K, Nukiwa T, Takahashi K, Takahashi H, Kira S (1994) Amylase mRNA transcripts in normal tissues and neoplasms: the implication of different expressions of amylase isogenes. J Cancer Res Clin Oncol 120:213–220

    Article  CAS  PubMed  Google Scholar 

  79. Seymour PA (2014) Sox9: a master regulator of the pancreatic program. Rev Diabet Stud 11:51–83

    Article  PubMed  PubMed Central  Google Scholar 

  80. Shen J, Person MD, Zhu J, Abbruzzese JL, Li D (2004) Protein expression profiles in pancreatic adenocarcinoma compared with normal pancreatic tissue and tissue affected by pancreatitis as detected by two-dimensional gel electrophoresis and mass spectrometry. Cancer Res 64:9018–9026

    Article  CAS  PubMed  Google Scholar 

  81. Storr SJ, Zaitoun AM, Arora A, Durrant LG, Lobo DN, Madhusudan S, Martin SG (2012) Calpain system protein expression in carcinomas of the pancreas, bile duct and ampulla. BMC Cancer 12:511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Strobel O, Rosow DE, Rakhlin EY, Lauwers GY, Trainor AG, Alsina J, Fernández-Del Castillo C, Warshaw AL, Thayer SP (2010) Pancreatic duct glands are distinct ductal compartments that react to chronic injury and mediate Shh-induced metaplasia. Gastroenterology 138:1166–1177

    Article  PubMed  Google Scholar 

  83. Su Y, Jono H, Misumi Y, Senokuchi T, Guo J, Ueda M, Shinriki S, Tasaki M, Shono M, Obayashi K, Yamagata K, Araki E, Ando Y (2012) Novel function of transthyretin in pancreatic alpha cells. FEBS Lett 586:4215–4222

    Article  CAS  PubMed  Google Scholar 

  84. Sun TT (2006) Altered phenotype of cultured urothelial and other stratified epithelial cells: implications for wound healing. Am J Physiol Renal Physiol 291:F9–F21

    Article  CAS  PubMed  Google Scholar 

  85. Talbot NC, Caperna TJ (1998) Selective and organotypic culture of intrahepatic bile duct cells from adult pig liver. In Vitro Cell Dev Biol Anim 34A:785–798

    Article  Google Scholar 

  86. Talbot NC, Paape MJ (1996) Continuous culture of pig tissue-derived macrophages. Methods Cell Sci 18:315–327

    Article  Google Scholar 

  87. Talbot NC, Shannon AE, Phillips CE, Garrett WM (2017) Derivation and characterization of a pig embryonic-stem-cell-derived exocrine pancreatic cell line. Pancreas 46:789–800

    Article  CAS  PubMed  Google Scholar 

  88. Talbot NC, Shannon AE, Phillips CE, Garrett WM (2018) Feeder-cell-independent culture of the pig embryonic stem cell-derived exocrine pancreatic cell line, PICM-31. In Vitro Cell Dev Biol Anim 54:321–330

    Article  CAS  PubMed  Google Scholar 

  89. Tezel E, Nagasaka T, Tezel G, Kaneko T, Takasawa S, Okamoto H, Nakao A (2004) REG I as a marker for human pancreatic acinoductular cells. Hepatogastroenterology 51:91–96

    PubMed  Google Scholar 

  90. Tooze J, Hollinshead M, Hensel G, Kern HF, Hoflack B (1991) Regulated secretion of mature cathepsin B from rat exocrine pancreatic cells. Eur J Cell Biol 56:187–200

    CAS  PubMed  Google Scholar 

  91. Truty MJ, Smoot RL (2008) Animal models in pancreatic surgery: a plea for pork. Pancreatology 8:546–550

    Article  PubMed  Google Scholar 

  92. Tsao MS, Duguid WP (1987) Establishment of propagable epithelial cell lines from normal adult rat pancreas. Exp Cell Res 168:365–375

    Article  CAS  PubMed  Google Scholar 

  93. Tsutsumi K, Sato N, Tanabe R, Mizumoto K, Morimatsu K, Kayashima T, Fujita H, Ohuchida K, Ohtsuka T, Takahata S, Nakamura M, Tanaka M (2012) Claudin-4 expression predicts survival in pancreatic ductal adenocarcinoma. Ann Surg Oncol 19(Suppl 3):S491–S499

    Article  PubMed  Google Scholar 

  94. Vinter-Jensen L, Juhl CO, Teglbjaerg PS, Poulsen SS, Dajani EZ, Nexø E (1997) Systemic treatment with epidermal growth factor in pigs induces ductal proliferations in the pancreas. Gastroenterology 113:1367–1374

    Article  CAS  PubMed  Google Scholar 

  95. Vishwanatha JK, Chiang Y, Kumble KD, Hollingsworth MA, Pour PM (1993) Enhanced expression of annexin II in human pancreatic carcinoma cells and primary pancreatic cancers. Carcinogenesis 14:2575–2579

    Article  CAS  PubMed  Google Scholar 

  96. Wada R, Ogawa K, Yamaguchi T, Tanizaki T, Matsumoto M (2005) Intercalated duct cell is starting point in development of pancreatic ductal carcinoma? J Carcinog 4:9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Wang Y, Lanzoni G, Carpino G, Cui CB, Dominguez-Bendala J, Wauthier E, Cardinale V, Oikawa T, Pileggi A, Gerber D, Furth ME, Alvaro D, Gaudio E, Inverardi L, Reid LM (2013) Biliary tree stem cells, precursors to pancreatic committed progenitors: evidence for possible life-long pancreatic organogenesis. Stem Cells 31:1966–1979

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Wang YJ, Park JT, Parsons MJ, Leach SD (2015) Fate mapping of ptf1a-expressing cells during pancreatic organogenesis and regeneration in zebrafish. Dev Dyn 244:724–735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Watanabe K, Ueno M, Kamiya D, Nishiyama A, Matsumura M, Wataya T, Takahashi JB, Nishikawa S, Nishikawa S, Muguruma K, Sasai Y (2007) A ROCK inhibitor permits survival of dissociated human embryonic stem cells. Nat Biotechnol 25:681–686

    Article  CAS  PubMed  Google Scholar 

  100. Westmoreland JJ, Wang Q, Bouzaffour M, Baker SJ, Sosa-Pineda B (2009) Pdk1 activity controls proliferation, survival, and growth of developing pancreatic cells. Dev Biol 334:285–298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Wiśniewski JR, Zougman A, Nagaraj N, Mann M (2009) Universal sample preparation method for proteome analysis. Nat Methods 6:359–362

    Article  CAS  Google Scholar 

  102. Xuan S, Borok MJ, Decker KJ, Battle MA, Duncan SA, Hale MA, Macdonald RJ, Sussel L (2012) Pancreas-specific deletion of mouse Gata4 and Gata6 causes pancreatic agenesis. J Clin Invest 122:3516–3528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Yamaguchi J, Liss AS, Sontheimer A, Mino-Kenudson M, Castillo CF, Warshaw AL, Thayer SP (2015) Pancreatic duct glands (PDGs) are a progenitor compartment responsible for pancreatic ductal epithelial repair. Stem Cell Res 15:190–202

  104. Yamaguchi N, Yamamura Y, Koyama K, Ohtsuji E, Imanishi J, Ashihara T (1990) Characterization of new human pancreatic cancer cell lines which propagate in a protein-free chemically defined medium. Cancer Res 50:7008–7014

  105. Yonezawa S, Sueyoshi K, Nomoto M, Kitamura H, Nagata K, Arimura Y, Tanaka S, Hollingsworth MA, Siddiki B, Kim YS, Sato E (1997) MUC2 gene expression is found in noninvasive tumors but not in invasive tumors of the pancreas and liver: its close relationship with prognosis of the patients. Hum Pathol 28:344–352

    Article  CAS  PubMed  Google Scholar 

  106. Yu JX, Chao L, Chao J (1994) Prostasin is a novel human serine proteinase from seminal fluid. Purification, tissue distribution, and localization in prostate gland. J Biol Chem 269:18843–18848

    CAS  PubMed  Google Scholar 

  107. Zhou Q, Law AC, Rajagopal J, Anderson WJ, Gray PA, Melton DA (2007) A multipotent progenitor domain guides pancreatic organogenesis. Dev Cell 13:103–114

    Article  CAS  PubMed  Google Scholar 

  108. Zhu GH, Huang C, Qiu ZJ, Liu J, Zhang ZH, Zhao N, Feng ZZ, Lv XH (2011) Expression and prognostic significance of CD151, c-Met, and integrin alpha3/alpha6 in pancreatic ductal adenocarcinoma. Dig Dis Sci 56:1090–1098

  109. Zhu Y, Xu G, Patel A, McLaughlin MM, Silverman C, Knecht K, Sweitzer S, Li X, McDonnell P, Mirabile R, Zimmerman D, Boyce R, Tierney LA, Hu E, Livi GP, Wolf B, Abdel-Meguid SS, Rose GD, Aurora R, Hensley P, Briggs M, Young PR (2002) Cloning, expression, and initial characterization of a novel cytokine-like gene family. Genomics. 80:144–150

Download references

Acknowledgments

The authors thank Ms. Caitlin Phillips for her assistance in primer design and for preliminary RT-PCR analysis of the PICM-31D cell line.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Neil C. Talbot.

Ethics declarations

Care and treatment of pigs in this study were approved by the Institutional Animal Care and Use Committee of the U.S. Department of Agriculture, Beltsville Agricultural Research Center, Beltsville, MD.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Mention of trade names or commercial products in this publication is solely for the purposes of providing specific information and does not imply recommendation or endorsement by the U.S. Department of Agriculture.

Editor: Tetsuji Okamoto

Electronic supplementary material

Supplementary Figure 1
figure7

Semi-quantitative RT-PCR assay of the expression of pancreas duct cell genes and uroplakin genes in fetal pig pancreas tissue (FP), weanling pig (21-d old) pancreas tissue (WP), fetal pig intestinal tissue (FI), and weanling pig intestinal tissue (WI). Weanling pig intestine mRNA was used for the -RT control. (PNG 210 kb)

High resolution image (TIF 2681 kb)

Supplementary Table 1

(DOCX 18 kb)

ESM 1

Supplementary Data Sheet 1 (DOCX 862 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Talbot, N.C., Shannon, A.E. & Garrett, W.M. Pancreatic duct-like cell line derived from pig embryonic stem cells: expression of uroplakin genes in pig pancreatic tissue. In Vitro Cell.Dev.Biol.-Animal 55, 285–301 (2019). https://doi.org/10.1007/s11626-019-00336-5

Download citation

Keywords

  • Cell line
  • Duct
  • Feeder cells
  • Pancreas
  • Porcine
  • STO