Notch2-positive progenitors with the intrinsic ability to give rise to pancreatic ductal cells

Kwang M. Lee, Hiroaki Yasuda, Michael A Hollingsworth, Michel M Ouellette

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Pancreatic adenocarcinomas display foci of duct-like structures that are positive for markers of pancreatic ductal cells. The development of these tumors is promoted by conditions leading to acinar-to-ductal metaplasia, a process by which acinar cells are replaced by ductal cells. Acinar-to-ductal metaplasia has recently been shown to proceed through intermediary cells expressing Nestin. To create an in vitro system to study pancreatic adenocarcinomas, we had used an hTERT cDNA to immortalize primary cells of the human pancreas. In this report, we show that the immortalized cells, termed hTERT-HPNE cells, have the ability to differentiate to pancreatic ductal cells. Exposing hTERT-HPNE cells to sodium butyrate and 5-aza-2′-deoxycytidine lead to the formation of pancreatic ductal cells marked by the expression of MDR-1, carbonic anhydrase II, and the cytokeratins 7, 8, and 19. hTERT-HPNE cells were found to have properties of the intermediary cells formed during acinar-to-ductal metaplasia, which included their undifferentiated phenotype, expression of Nestin, evidence of active Notch signaling, and ability to differentiate to pancreatic ductal cells. These results provide further evidence for the presence in the adult pancreas of a precursor of ductal cells. hTERT-HPNE cells should provide a useful model to study acinar-to-ductal metaplasia and the role played by this process in pancreatic cancer development.

Original languageEnglish (US)
Pages (from-to)1003-1012
Number of pages10
JournalLaboratory Investigation
Volume85
Issue number8
DOIs
StatePublished - Aug 1 2005

Fingerprint

Metaplasia
Nestin
decitabine
Pancreas
Adenocarcinoma
Carbonic Anhydrase II
Keratin-8
Keratin-7
Keratin-19
Butyric Acid
Acinar Cells
Pancreatic Neoplasms
Complementary DNA
Phenotype
Neoplasms

Keywords

  • Duct
  • Epigenetic
  • Metaplasia
  • Nestin
  • Notch
  • Pancreas

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Notch2-positive progenitors with the intrinsic ability to give rise to pancreatic ductal cells. / Lee, Kwang M.; Yasuda, Hiroaki; Hollingsworth, Michael A; Ouellette, Michel M.

In: Laboratory Investigation, Vol. 85, No. 8, 01.08.2005, p. 1003-1012.

Research output: Contribution to journalArticle

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