Importance of visceral adipose tissue inflammation on pancreatic neoplasia

• Applicant: Dr. Andrea Isabella Schmidt
• Subject Area: General and Visceral Surgery
• Term: from 2015 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 280662899

Inflammation is widely recognized as a major contributing factor for the development of cancer, including pancreatic cancer. In patients suffering from chronic pancreatitis over 20 years 4% were diagnosed with malignant pancreatic neoplasia. Obesity is another well-known risk factor for development of different malignancies. Although the precise underlying mechanism has not been identified yet, it is thought that the obesity-associated inflammation of adipose tissue, in particular of the visceral adipose tissue, plays a significant role in the development of gastrointestinal cancers, including pancreatic cancer. Over the past years, mouse models of pancreatic cancer have clearly implicated tissue inflammation as a contributing or causative factor for pancreatic cancer. This project is designed to 1) investigate adipose and pancreatic tissue inflammation as potential promoting factors for pancreatic cancer development using the conditional KrasG12D mouse model. KrasG12D mutant mice will be fed either a control diet or a diet high in fats and calories (HFCD) for various time periods up to 12 months. Tissue inflammation (pancreas and various visceral adipose tissue depots) will be evaluated histologically. Infiltrating inflammatory cells will be quantified and characterized by flow cytometry. Inflammatory cytokine production will be measured by multiplex analysis. In addition, neoplastic changes in the pancreas will be determined. 2) In addition, the significance of adipose tissue inflammation to pancreatic cancer development will be clarified using knockout animals. Trip-Br2-null and HSL-null mice will be crossed into the KrasG12D mouse model. These knockout models will conclusively demonstrate whether diet-induced promotion of pancreatic cancer in this model is caused by adipose tissue inflammation or potentially by direct effects of the diet.Successful completion of the proposed studies will demonstrate the importance of diet-induced adipose tissue inflammation to pancreatic cancer development and will provide the basis for further interventional strategies aimed at reducing adipose tissue inflammation and as a consequence pancreatic cancer development.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Guido Eibl