Oral Presentation Australasian Extracellular Vesicles Conference 2018

Oncogenic and non-malignant pancreatic exosome cargo reveal distinct expression of oncogenic and prognostic factors involved in tumour invasion and metastasis (#31)

Aikaterini Emmanouilidi 1 , Dino Paladin 1 , David W Greening 2 , Peter Meikle 3 , Marco Falasca 1
  1. School of Pharmacy & Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia, Australia
  2. Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia
  3. Baker Heart & Diabetes Institute, Melbourne , Victoria , Australia

Exosomes are increasingly being recognized as contributing factors in many diseases, and their potential as biomarkers and therapeutics is rapidly emerging. With survival rates of pancreatic cancer patients remaining consistently low, in an effort to understand the progression and identification of circulating markers of pancreatic cancer (PaCa), we isolated exosomes from malignant and non-malignant pancreatic cell models and performed proteomic analysis on both isolated exosomes and corresponding parental cells. Here we demonstrate the upregulation of key known malignant factors including various cell invasive and metastatic components, in addition to proteins known to correlate with poor prognosis (GPRC5A, PRSS23, and ITGA3). We further identify known modulators of pre-metastatic niche formation including factors NCSTN, ANXA1 and S100A4 and a selective enrichment / downregulation of alternative splicing regulators in cancer cells and exosomes (SR proteins and hnRNPs), as well as proteins implicated in lipid metabolism. To further investigate this, we performed lipidomic analysis of a number of malignant and non-malignant pancreatic cell models and their derived exosomes. Lipids have been proposed as potential biomarkers for many forms of cancer, and in this case pancreatic cancer - derived exosomes exhibited a great enrichment in free and esterified cholesterol. This thorough proteomic and lipidomic analysis allowed us to detect novel proteins that can be excellent prognostic biomarkers, and at the same time determine the major lipid classes which comprise the specific lipid signature for this malignancy, compared to others.