Islet amyloid polypeptide does not suppress pancreatic cancer

Austin J. Taylor; Evgeniy Panzhinskiy; Paul C. Orban; Francis C. Lynn; David F. Schaeffer; James D. Johnson; Janel L. Kopp; C. Bruce Verchere

Molecular Metabolism (Feb 2023)

Islet amyloid polypeptide does not suppress pancreatic cancer

Austin J. Taylor,
Evgeniy Panzhinskiy,
Paul C. Orban,
Francis C. Lynn,
David F. Schaeffer,
James D. Johnson,
Janel L. Kopp,
C. Bruce Verchere

Affiliations

Austin J. Taylor: BC Children's Hospital Research Institute, Vancouver, BC, Canada; Centre for Molecular Medicine and Therapeutics, Vancouver, BC, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, BC, Canada
Evgeniy Panzhinskiy: Life Sciences Institute, University of British Columbia, BC, Canada; Department of Biochemistry, University of British Columbia, BC, Canada
Paul C. Orban: BC Children's Hospital Research Institute, Vancouver, BC, Canada; Centre for Molecular Medicine and Therapeutics, Vancouver, BC, Canada; Department of Surgery, University of British Columbia, BC, Canada
Francis C. Lynn: BC Children's Hospital Research Institute, Vancouver, BC, Canada; Department of Surgery, University of British Columbia, BC, Canada; Department of Cellular and Physiological Sciences, University of British Columbia, BC, Canada
David F. Schaeffer: Department of Pathology and Laboratory Medicine, University of British Columbia, BC, Canada; Pancreas Centre BC, Vancouver, BC, Canada
James D. Johnson: Life Sciences Institute, University of British Columbia, BC, Canada; Department of Cellular and Physiological Sciences, University of British Columbia, BC, Canada
Janel L. Kopp: Life Sciences Institute, University of British Columbia, BC, Canada; Department of Cellular and Physiological Sciences, University of British Columbia, BC, Canada
C. Bruce Verchere: BC Children's Hospital Research Institute, Vancouver, BC, Canada; Centre for Molecular Medicine and Therapeutics, Vancouver, BC, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, BC, Canada; Department of Surgery, University of British Columbia, BC, Canada; Corresponding author. BC Children's Hospital Research Institute, Vancouver, BC, Canada.

Journal volume & issue: Vol. 68
p. 101667

Abstract

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Objectives: Pancreatic cancer risk is elevated approximately two-fold in type 1 and type 2 diabetes. Islet amyloid polypeptide (IAPP) is an abundant beta-cell peptide hormone that declines with diabetes progression. IAPP has been reported to act as a tumour-suppressor in p53-deficient cancers capable of regressing tumour volumes. Given the decline of IAPP during diabetes development, we investigated the actions of IAPP in pancreatic ductal adenocarcinoma (PDAC; the most common form of pancreatic cancer) to determine if IAPP loss in diabetes may increase the risk of pancreatic cancer. Methods: PANC-1, MIA PaCa-2, and H1299 cells were treated with rodent IAPP, and the IAPP analogs pramlintide and davalintide, and assayed for changes in proliferation, death, and glycolysis. An IAPP-deficient mouse model of PDAC (Iapp−/−; Kras+/LSL-G12D; Trp53flox/flox; Ptf1a+/CreER) was generated for survival analysis. Results: IAPP did not impact glycolysis in MIA PaCa-2 cells, and did not impact cell death, proliferation, or glycolysis in PANC-1 cells or in H1299 cells, which were previously reported as IAPP-sensitive. Iapp deletion in Kras+/LSL-G12D; Trp53flox/flox; Ptf1a+/CreER mice had no effect on survival time to lethal tumour burden. Conclusions: In contrast to previous reports, we find that IAPP does not function as a tumour suppressor. This suggests that loss of IAPP signalling likely does not increase the risk of pancreatic cancer in individuals with diabetes.

Published in Molecular Metabolism

ISSN: 2212-8778 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine
Website: https://www.journals.elsevier.com/molecular-metabolism/

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