Abstract 4002: Exploring the miRNA and proteomic contents of exosomes isolated from rhabdomyosarcoma tumor cells to understand their paracrine signaling

Abstract

Abstract Rhabdomyosarcoma (RMS) is an aggressive childhood soft tissue tumor, with two distinct subtypes, alveolar (ARMS) and embryonal (ERMS) histologies. The alveolar subtype is characterized by a specific translocation PAX-FOXO, the protein product of which is thought to contribute to its aggressive and metastatic behaviour. Exosomes are small membranous vesicles (30-100 nm in diameter) secreted into body fluids by multiple cell types, including tumor cells. Tumor exosomes contain intact and functional protein and microRNA that can alter the cellular environment to favor tumor growth. We hypothesize that the PAX-FOXO fusion protein results in specific effects on exosome cargo and biology, contributing to the invasive and metastatic potential of ARMS cells. Thus proteomic and molecular profiling of their exosomes may increase our understanding of the role of exosomes in sarcoma progression and may lead to discovery of useful biomarkers. In the present study, we used miRNA array profiling to identify interesting exosomal miRNA expressed commonly in two different ARMS cell lines. We also used proteomic analysis and discovered differentially expressed ARMS exosomal proteins. Importantly, functional studies revealed that normal fibroblasts acquired invasion and migration ability through molecules transported in ARMS cell-derived exosomes. Our results indicate that ARMS-derived exosomes have unique gene expression signatures,miRNA and proteomics profiles which will help our understanding of sarcoma biogenesis and that could be used as biomarkers for early diagnosis of ARMS, and targets for therapeutic intervention. Citation Format: Sandra E. Ghayad, Farah Ghamloush, Raya Saab. Exploring the miRNA and proteomic contents of exosomes isolated from rhabdomyosarcoma tumor cells to understand their paracrine signaling. [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 4002. doi:10.1158/1538-7445.AM2014-4002