title: Impact of diabetes type II and chronic inflammation on pancreatic cancer.
abstract: BACKGROUND
  We explored if known risk factors for pancreatic cancer such as type II diabetes and chronic inflammation, influence the pathophysiology of an established primary tumor in the pancreas and if administration of metformin has an impact on tumor growth.
  
  
  METHODS
  Pancreatic carcinomas were assessed in a syngeneic orthotopic pancreas adenocarcinoma model after injection of 6606PDA cells in the pancreas head of either B6.V-Lep(ob/ob) mice exhibiting a type II diabetes-like syndrome or normoglycemic mice. Chronic pancreatitis was then induced by repetitive administration of cerulein. Cell proliferation, cell death, inflammation and the expression of cancer stem cell markers within the carcinomas was evaluated by immunohistochemistry. In addition, the impact of the antidiabetic drug, metformin, on the pathophysiology of the tumor was assessed.
  
  
  RESULTS
  Diabetic mice developed pancreatic ductal adenocarcinomas with significantly increased tumor weight when compared to normoglycemic littermates. Diabetes caused increased proliferation of cancer cells, but did not inhibit cancer cell necrosis or apoptosis. Diabetes also reduced the number of Aldh1 expressing cancer cells and moderately decreased the number of tumor infiltrating chloracetate esterase positive granulocytes. The administration of metformin reduced tumor weight as well as cancer cell proliferation. Chronic pancreatitis significantly diminished the pancreas weight and increased lipase activity in the blood, but only moderately increased tumor weight.
  
  
  CONCLUSIONS
  We conclude that diabetes type II has a fundamental influence on pancreatic ductal adenocarcinoma by stimulating cancer cell proliferation, while metformin inhibits cancer cell proliferation. Chronic inflammation had only a minor effect on the pathophysiology of an established adenocarcinoma.
authors.affiliation: Institute for Experimental Surgery, Rostock University Medical Center, Schillingallee 69a, 18057, Rostock, Germany. dietmar.zechner@uni-rostock.de.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Zechner
authors.affiliation: Institute for Experimental Surgery, Rostock University Medical Center, Schillingallee 69a, 18057, Rostock, Germany. tobias.radecke@icloud.com.
authors.forename: Tobias
authors.initials: T
authors.lastname: Radecke
authors.affiliation: Institute for Experimental Surgery, Rostock University Medical Center, Schillingallee 69a, 18057, Rostock, Germany. jonasamme@gmx.de.
authors.forename: Jonas
authors.initials: J
authors.lastname: Amme
authors.affiliation: Institute for Experimental Surgery, Rostock University Medical Center, Schillingallee 69a, 18057, Rostock, Germany. florian_buertin@gmx.de.
authors.forename: Florian
authors.initials: F
authors.lastname: Bürtin
authors.affiliation: Institute for Experimental Surgery, Rostock University Medical Center, Schillingallee 69a, 18057, Rostock, Germany. a_c.albert@yahoo.de.
authors.forename: Ann-Christin
authors.initials: AC
authors.lastname: Albert
authors.affiliation: Department of General, Visceral, Thoracic and Vascular Surgery, University Medicine Greifswald, Ernst-Moritz-Arndt-University, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany. partecke@uni-greifswald.de.
authors.forename: Lars Ivo
authors.initials: LI
authors.lastname: Partecke
authors.affiliation: Institute for Experimental Surgery, Rostock University Medical Center, Schillingallee 69a, 18057, Rostock, Germany. brigitte.vollmar@med.uni-rostock.de.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Vollmar
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D016923:Cell Death; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002908:Chronic Disease; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000473:pathology; D004195:Disease Models, Animal; D015870:Gene Expression; D007249:Inflammation / Q000150:complications* / Q000473:pathology; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D014411:Neoplastic Stem Cells / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D050500:Pancreatitis, Chronic / Q000150:complications / Q000473:pathology; D050697:Retinal Dehydrogenase; D012307:Risk Factors; D047368:Tumor Burden / Q000187:drug effects; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
chemical_list: D014746:Vimentin; D008687:Metformin; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase