Abstract 390: Increased orthotopic pancreatic tumor cell growth in obese mice

Abstract

Abstract Pancreatic cancer remains one of the eight deadliest cancers due to its late detection and high propensity to metastasize. Increased risk for the development of pancreatic cancer has been associated with obesity, type II diabetes and pancreatitis. The contribution of adipocytes and adipokines to pancreatic cancer progression remains largely unknown and requires further analysis. We hypothesize that increased pancreatic fat compromises the pancreatic microenvironment and increases primary tumor growth as well as metastasis. The condition of non-alcoholic fatty pancreatic disease has been characterized in humans as well as mice and lymph node positive patients were found to have increased pancreatic fat1,2. Adipose secreted cytokines, also known as adipokines, have both been implicated in various aspects of cancer cell survival, growth, and migration. To understand the influence that increased pancreatic fat has on the growth of tumors, both primary and metastatic, we have investigated a high fat diet induced murine model. Male mice fed a 42% fat diet for three months develop increased inter-pancreatic and intra-pancreatic fat as well as acute localized pancreatitis when compared to mice fed a 13% fat diet. To test the affect of pancreatic fat on tumor cells, we used an orthotopic tumor injection model to determine the rate of primary tumor growth and progression to metastasis. Further, we are implementing the use of Panc02-luciferase tagged cells to monitor and measure pancreatic tumor growth over time and to detect the presence of metastases in the liver and/or lungs. Preliminary evidence has confirmed that orthotopic tumors grown in obese mice led to an increased tumor size as well as massive expansion of tumor cells into the interpancreatic fat. In conclusion, increased pancreatic fat promotes the growth of orthotopically implanted murine tumor cells, yet the molecular mechanisms remain undetermined. 1. Mathur, A. et al. J Am Coll Surg. 2009 May;208(5):989-94. 2. Mathur, A. et al. HPB (Oxford). 2007;9(4):312-8. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 390. doi:10.1158/1538-7445.AM2011-390