4.4 Article

Characterization of primary cilia and hedgehog signaling during development of the human pancreas and in human pancreatic duct cancer cell lines

Journal

DEVELOPMENTAL DYNAMICS
Volume 237, Issue 8, Pages 2039-2052

Publisher

WILEY
DOI: 10.1002/dvdy.21610

Keywords

primary cilia; pancreas; exocrine duct; development; cancer; Hedgehog signaling; Smoothened; Patched; Gli2; Gli3

Funding

  1. Lundbeck Foundation
  2. Novo Nordisk/Novozymes Foundation
  3. Danish Science Research Council
  4. Department of Biology, University of Copenhagen
  5. National Institute of Health

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Hedgehog (Hh) signaling controls pancreatic development and homeostasis; aberrant Hh signaling is associated with several pancreatic diseases. Here we investigated the link between Hh signaling and primary cilia in the human developing pancreatic ducts and in cultures of human pancreatic duct adenocarcinoma cell lines, PANC-1 and CFPAC-1. We show that the onset of Hh signaling from human embryogenesis to fetal development is associated with accumulation of Hh signaling components Smo and Gli2 in duct primary cilia and a reduction of Gli3 in the duct epithelium. Smo, Ptc, and Gli2 localized to primary cilia of PANC-1 and CFPAC-1 cells, which may maintain high levels of nonstimulated Hh pathway activity. These findings indicate that primary cilia are involved in pancreatic development and postnatal tissue homeostasis.

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