Results: Biochemical and imaging assays showed that reduced levels of 5-HT prevented Rac1 activation both in vitro and in vivo. Inhibition of 5-HT uptake completely abolished ADM formation in 3D culture-system and significantly reduced pancreatic cancer cell migration, without affecting cell viability. Importantly, pharmacological treatment of Kras G12D mice with SERTi significantly reduced ADM and PanIN lesion formation without apparent drug toxicity. Conclusion: Our data indicate that cytoskeletal remodeling, depen- dent on i5-HT, is critical for the formation of ADM lesions and cancer cell migration likely through Rac1 activation. Given the aggressive nature of pancreatic ductal adenocarcinoma (PDAC), we are currently investigating the potential of SERTi as a novel therapeutic strategy to target cancer development and invasiveness. 1167. Role of PAK4 in pancreas development and pancreatic cancer progression Miao Zhao 1 , Tania Costa 1 , Ting Zhuang 1 , Rainer Heuchel 2 , Matthias L€ ohr 2 , Staffan Str€ ombald 1 1 Karolinska Institutet, Department of Biosciences and Nutrition, Sweden 2 Karolinska Institutet, Department of CLINTECH, Sweden Introduction: P21-activated kinase 4 (PAK4) is a serine/threonine ki- nase that plays a functional role in several vital cellular processes including cell migration, cell survival and mitosis. PAK4 is overexpressed and amplified in different pancreatic cancer cell lines and a fraction of pancreatic ductal adenocarcinoma patients. Aims: It appears important to elucidate the potential functions of PAK4 in pancreatic cancer progression in vivo. Materials & methods: In order to elucidate the role of PAK4 in pancreatic cancer progression, we firstly address the role of PAK4 in pancreas development. We setup a mouse model lacking PAK4 specifically in the pancreas using the PDX-cre crossed with PAK4F/F. Further, the Pdx1- cre; LSL-Kras G12D pancreatic cancer mouse model have been crossed with PAK4 F/F mice to investigate the possible role of PAK4 in pancreatic cancer progression. Results: So far, we did not observe any effect of PAK4 deletion on pancreas development. All the pups were born at the expected genotype ratio, and there is no difference in body weight or pancreas weight. H & E stainings display no recognisable differences between Pdx1-cre; PAK4 F/F and age-matched PAK4 F/F mice. Analysis of Pdx1-cre; LSL-Kras G12D, PAK4 mice is in progression. Conclusion: This study will elucidate the role of PAK4 in pancreatic cancer progression and determine the potential usefulness of PAK4 in- hibitors in pancreatic cancer therapy. 914. Identification of a novel a-ketoamide inhibitor as highly selective cathepsin S inhibitor with potentials against pancreatic cancer growth Jang-Yang Chang 1 , Wun-Shaing Chang 2 , Chien-Chang Huang 2 1 College of Medicine, National Cheng Kung University, Taiwan 2 National Institute of Cancer Research, National Health Research Institutes, Taiwan Introduction: Degradation of surrounding matrix components by secreted proteolytic enzymes play an important role in the development of various malignant tumors. Recent study indicate that cathepsin S, the crucial cysteine protease, is up-regulated in pancreatic and other tumors and secreted into the extracellular milieu for extracellular matrix degradation. Aims: We designed and generated a series of cathepsin S inhibitors to test their anti-proliferative activity against pancreatic cancers and study their mechanism of action. Materials & methods: A series of new synthesized small molecule compounds which bearing an a-ketoamide warhead were evaluated their inhibitory ability against cathepsin S. Kinetic analysis were used to reveal the Ki values and specificities. Several pancreatic cell lines were used to test anti-proliferative activity of these compounds. Cell invasive and migratory assays were also performed. Orthotopic animal model were used to determine the antitumor effect in vivo. Results: We characterized a novel a-ketoamide inhibitor which exerts low Ki values and high specificity against cathepsin S activities. Targeting cathepsin S could induce autophagy followed by ROS generation and trigger cell apoptosis. Inhibiting cathepsin S ac- tivities not only reduces fibronectin degradation but also attenuates the migration and invasive abilities in various pancreatic cell lines. The results of the effect of candidate compound showed that a novel cathepsin S inhibitor can effective reduce the spread of pancreatic tu- mor cells and consequently prolong mice survival in orthotopic animal model. Conclusion: These results suggest that cathepsin S inhibitor could have potential as antitumor agent against pancreatic cancer. 1170. Carboxyl-ester lipase (CEL) as biomarker in pancreas cancer: Characterization of the monoclonal antibody 16D10 targeting pancre- atic neoplastic cells and cross-reacting with histo-blood group A antigens Khadija El Jellas 1 , Heike Immervoll 2 , Ole Steffensen 2 , Bente Berg Johansson 3 , Karianne Fjeld 3 , Dominique Lombardo 4 , P  ll Rasmus Nj rlstad 3 , Eric Mas 4 , Anders Molven 1 1 Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Norway 2 Department of Pathology, Ålesund Hospital, Ålesund, Norway 3 KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Norway 4 Centre de Recherche en Oncologie Biologique et Oncopharmacologie, Marseille, France Introduction: Carboxyl-ester lipase (also denoted bile salt-dependent lipase) is a digestive enzyme with expression mainly restricted to pancreatic acinar cells. The globular part of CEL is N-glycosylated whereas its mucin-like carboxyl-terminus is highly O-glycosylated. The monoclonal antibody mAb16D10 (Benko€ el 2009) was raised against immunoprecipi- tated CEL from pancreatic juice of a cancer case and recognizes disease- specific glycan structures of the pancreas, including a glycotope associated with the mucinous tail of a CEL glycovariant. Aims: To further characterize the 16D10 glycotope in pancreatic cancer. Materials & methods: Tissue samples and pancreatic juice were collected from patients from Haukeland University Hospital, Norway. Immunohistochemistry and Western blot were performed with mAb16D10. In situ hybridization (ISH) was done with a probe covering CEL exon 2-7. Results: In pancreatic tissue samples, mAb16D10 showed cross-reac- tivity with histo-blood group A antigens in endothelium, erythrocytes and acinar cells. The 16D10 glycotope was present in neoplastic cells (but not in normal pancreatic tissue) from all blood group B and O pancreatic cancer cases examined. Langerhans islets, which normally do not express CEL, exhibited mAb16D10 positivity when located in the vicinity of cancerous tissue. ISH did not detect CEL mRNA in the cancer cells. Parallel immuno- blotting of pancreatic juice with mAb16D10 and an anti-CEL antibody showed bands of different molecular weights. Conclusion: It is possible that the mAb16D10-positive glycotope is carried not only by the CEL protein but also by a CEL interaction partner. Further work is needed to determine the identity and the functional im- plications of the 16D10 glycan. Abstracts / Pancreatology 15 (2015) S1eS141 S34