PROTEOMIC CHARACTERIZATION OF EXOSOMES SHED BY MYELOID-DERIVED SUPPRESSOR CELLS
Burke, Meghan Catherine
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Exosomes are a class of extracellular vesicles that have been shown to contribute to metastasis when derived from tumor cells. Myeloid-derived suppressor cells (MDSC) are an immature population of myeloid cells that accumulate in the tumor microenvironment and inhibit anti-tumor immunity. Given the role of the source cells, it is our hypothesis that MDSC-derived exosomes may contribute to or mediate the effects of MDSC in the tumor microenvironment. The goal of this work is to use mass-spectrometry based proteomics to characterize exosomes produced by MDSC that are induced by 4T1 mammary carcinoma. The protein content of the exosomes will be analyzed to determine if the exosomal proteome is representative of the parental cells or if it reflects active protein sorting. Increased inflammation in the tumor microenvironment is associated with an increased population of MDSC, which further increases the level of immune suppression. Here, the relative change in abundance of exosomal proteins under a heightened level of inflammation in the tumor microenvironment will be performed using the spectral count method. While it is known that exosomes first form through invagination at the plasma membrane, the mechanism(s) through which the protein cargo is sorted into exosomes remains poorly understood. Given the role of ubiquitination in protein localization and trafficking, immunoaffinity enrichment coupled to mass spectrometry has been employed to identify exosomal proteins that carry this modification. Identification of the substrate proteins in MDSC-derived exosomes may provide insight into exosome formation and/or function.