Role of S100A8/A9 in the cross-talk between cancer cells and stroma-associated cells

Abstract

s / Pancreatology 12 (2012) 502–597 589 1 Tampere Pancreas Laboratory, Tampere University Hospital, Tampere, Finland Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland Department of Gastroenterological Surgery, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan Objectives: Studies with PANC-1 imply that autophagymay be induced in pancreatic ductal adenocarcinoma (PDA). Investigating the role of autophagy in patients is challenging as the induction of autophagy in pancreatic tissue may be affected by cell death mechanisms taking place after the tissue specimens have been harvested. Eliminating this postharvesting distraction would be crucial when investigating this phenomenon. No such study about autophagy in PDA in patients exists. Our aim was to study, whether autophagy is 1) induced in PDA compared to healthy pancreatic tissue in patients, and 2) correspondent to the autophagic status of PANC-1 cells in vitro. Patients and methods: Pancreatic samples were retrieved in laparotomy from patients undergoing pancreato-duodenectomy. Core-needle biopsies from the center of histologically-confirmed PDA tumors and from healthy pancreas (within the area to be resected) were immediately snapfrozen and proteins were extracted by repeated freeze-thaw cycles. The degree of autophagy was analysed by Western blotting of LC3-II, and compared to the degree of autophagy in PANC-1 cells (in basal conditions and when treated with anticancer drugs (gemcitabine and 5-FU) +/autophagy inhibitor chloroquine). Results: Autophagy was significantly induced in PDA compared to healthy pancreatic tissue in patients. This resembled the autophagic status of PANC-1 cells under basal culture conditions. Conclusions: Autophagy is induced in PDA in patients similarly to PANC-1 cells. In PANC-1 cells chloroquine increases the cytotoxicity of 5FU and gemcitabine by inhibiting autophagy. Thus patients with PDA may benefit from therapy where anticancer drugs are combined with an autophagy inhibitor.