Proteomics analyses to identify targets within the tumor microenvironment

6^th International Conference on Biomarkers & Clinical Research

August 31-September 02, 2015 Toronto, Canada

Principe Simona

Princess Margaret Cancer Center, Canada

Posters-Accepted Abstracts: J Mol Biomark Diagn

Abstract :

Cancer-associated fibroblasts (CAFs) represent the most abundant cell type within the stroma and are key components involved in the regulation of carcinogenesis. During the development of cancer, CAFs create a supporting niche by maintaining a bidirectional crosstalk with epithelial cells, mediated by extracellular matrix components, cell-cell contact, classically secreted soluble factors and extracellular vesicles, such as exosomes. To investigate stromal heterogeneity in oral cancers and identify cancer-associated proteins, we employed a shotgun proteomics approach for a comprehensive analysis of CAF-derived proteins. We isolated matched pairs of human primary fibroblasts from oral cancers (CAFs) and adjacent tissue (AFs) and characterized them according to morphology, expression of myofibroblast markers and the ability to contract collagen matrices in vitro. We collected total lysates, conditioned media and exosomes and analyzed each sample by Ultra-High Pressure Liquid Chromatography (UHPLC) coupled to a Q-Exactive mass spectrometer. We applied quantitative proteomics to our comprehensive dataset of 4160 proteins, to select a list of ~200 proteins that are associated with a CAF-activated state. Our proteomic analyses provide a detailed overview of signaling factors, receptors and intracellular proteins, associated with the induction of a pro-tumorigenic stroma. Our findings highlight differential expression of key signal transduction molecules previously associated with cancer and we validated a CAF-specific exosomal and intracellular signature that can represent a novel source of promising biomarkers in oral cancer.

Biography :

Email: simonaprincipe83@gmail.com