Abstract A05: Proteomic analysis of exosome content changes induced by gemcitabine in pancreatic cancer stromal cells

Abstract

Abstract Despite recent advances in multimodality therapy, pancreatic ductal adenocarcinoma (PDAC) remains the 3rd leading cause of cancer-related deaths in the United States with a 5-year survival rate of 8%. One hallmark of this disease is desmoplasia that consist largely of stromal cells and extracellular matrix (ECM) proteins. The abundant stromal cells provide a unique tumor microenvironment that aid tumorigenesis. Unfortunately, there is little data on the mechanism underlying the stromal cells’ ability to impact chemoresistance in neighboring cancer cells in response to drug treatment. Exosomes are small vesicles secreted into the extracellular environment from cells and evidence is accumulating that exosomes play a key role in intercellular signaling. Researchers have focused on exosomes secreted from cancer cells, but the function of stromal exosomes has not been investigated, especially in pancreatic cancer. As stromal cells comprise the majority of the pancreatic tumor bulk, we hypothesize that stromal cell-derived exosomes help pancreatic cancer cells resist chemotherapy. Thus, it is critical to characterize the complex composition of stromal exosomes. In this study, we analyzed the proteomic content of exosomes collected from stromal cell lines created from PDAC patients. Furthermore, we also determined the change in exosomal proteomic composition after the patient-derived stromal cells were treated with gemcitabine, the current standard of care chemotherapy for patients with PDAC. Our studies have identified possible diagnostic and prognostic biomarkers and suggest novel molecular mechanism responsible for the tumor microenvironment’s ability to regulate chemoresistance in neighboring pancreatic cancer cells. Citation Format: Wei Huang, Peter Feist, Amanda Hummon, Reginald Hill.{Authors}. Proteomic analysis of exosome content changes induced by gemcitabine in pancreatic cancer stromal cells. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A05.