Exosomes are nanometer-sized extracellular vesicles that enable tumor cells to communicate with normal cells by transferring an assortment of cargo molecules to target cells. The exosome-mediated intercellular messaging system elicits a biological response in target cells leading to modulations in the tumor environment. Our results show that MSI driver mutations in a major signaling pathway, as exemplified by the TGFBR2 tumor suppressor, is potent to alter the protein profile and function of exosomes in MSI cancers.
From a clinical perspective, we seek to develop a serological detection tool for MSI tumors based on minimal-invasive extracellular vesicle isolation from patient blood samples to complement invasive tissue-based diagnostics. We have identified tumor-specific MSI mutation profiles in MSI cell-derived exosomes making these small vesicles promising targets for MSI liquid biopsy-based diagnostics.