Abstract 3594: Tumor microenvironment derived exosomes regulate prostate cancer metabolism

Abstract

Abstract Tumor microenvironment is composed of myofibroblasts, extracellular matrix, and many other cells. There are many ways for tumor to communicate with its microenvironment, such as growth factors, cytokines, chemokines and so on. Recent research has indicated that exosomes may serve an important role in communication between tumor and its microenvironment. Exosomes are nanosized particles secreted by cells and contain microRNA, metabolic enzymes, biomarker proteins, and some other functional components. We show a novel regulatory mechanism for modulating metabolism in prostate cancer cells by stromal cells. We found that exosomes from stromal fibroblast cells are uptaken by prostate cancer cells and they release RNAs, enzymes to regulate cancer cells metabolism. Our result shows that exosomes from patient derived fibroblasts enhance glucose uptake, lactate production and pyruvate uptake in prostate cancer cells. We further performed 13C based isotope labeling experiments using glucose and glutamine labeling to study metabolic rewiring induced in cancer cells by stromal exosomes. We found that exosomes downregulated mitochondria metabolism in prostate cancer cells. In summary, stroma derived exosomes enhanced Warburg effect in prostate cancer cells. Our findings can lead to the development of new therapeutics integrating tumor microenvironment and metabolic pathways in tumor cells. Citation Format: Hongyun Zhao, Lifeng Yang, Abhinav Achreja, Juan Marini, Donna Peehl, Deepak Nagrath. Tumor microenvironment derived exosomes regulate prostate cancer metabolism. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3594. doi:10.1158/1538-7445.AM2014-3594