title: Adipocytes enhance murine pancreatic cancer growth via a hepatocyte growth factor (HGF)-mediated mechanism.
abstract: BACKGROUND
  Obesity accelerates the development and progression of pancreatic cancer, though the mechanisms underlying this association are unclear. Adipocytes are biologically active, producing factors such as hepatocyte growth factor (HGF) that may influence tumor progression. We therefore sought to test the hypothesis that adipocyte-secreted factors including HGF accelerate pancreatic cancer cell proliferation.
  
  
  METHODS
  Murine pancreatic cancer cells (Pan02 and TGP-47) were grown in a) conditioned medium (CM) from murine F442A preadipocytes, b) HGF-knockdown preadipocyte CM, c) recombinant murine HGF at increasing doses, and d) CM plus HGF-receptor (c-met) inhibitor. Cell proliferation was measured using the MTT assay. ANOVA and t-test were applied; p < 0.05 considered significant.
  
  
  RESULTS
  Wild-type preadipocyte CM accelerated Pan02 and TGP-47 cell proliferation relative to control (59 ± 12% and 34 ± 12%, p < 0.01, respectively). Knockdown of preadipocyte HGF resulted in attenuated proliferation vs. wild type CM in Pan02 cells (35 ± 5% vs. 68 ± 14% greater than control; p < 0.05), but proliferation in TGP-47 cells remained unchanged. Recombinant HGF dose-dependently increased Pan02, but not TGP-47, proliferation (p < 0.05). Inhibition of HGF receptor, c-met, resulted in attenuated proliferation versus control in Pan02 cells, but not TGP-47 cells.
  
  
  CONCLUSIONS
  These experiments demonstrate that adipocyte-derived factors accelerate murine pancreatic cancer proliferation. In the case of Pan02 cells, HGF is responsible, in part, for this proliferation.
authors.affiliation: Department of Surgery, Indiana University School of Medicine, USA.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Ziegler
authors.affiliation: Division of Endocrinology, Department of Medicine, Indiana University School of Medicine, USA.
authors.forename: Robert V
authors.initials: RV
authors.lastname: Considine
authors.affiliation: Department of Surgery, Indiana University School of Medicine, USA.
authors.forename: Eben
authors.initials: E
authors.lastname: True
authors.affiliation: Department of Surgery, Indiana University School of Medicine, USA.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Swartz-Basile
authors.affiliation: Department of Surgery, Temple University School of Medicine, USA.
authors.forename: Henry A
authors.initials: HA
authors.lastname: Pitt
authors.affiliation: Department of Surgery, Indiana University School of Medicine, USA. Electronic address: nzyromsk@iupui.edu.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Zyromski
mesh_terms: D017667:Adipocytes / Q000502:physiology*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017228:Hepatocyte Growth Factor / Q000502:physiology*; D006801:Humans; D051379:Mice; D010190:Pancreatic Neoplasms / Q000473:pathology*; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors
chemical_list: D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met
keywords: Adipocytes; Hepatocyte growth factor; Obesity; Pancreatic cancer