Oncogenic Regulation of Extracellular Vesicle Proteome and Heterogeneity

Area of Science:

• Cancer Biology
• Cellular Communication
• Biomolecular Analysis

Background:

• Mutational and epigenetic events in cancer disrupt intercellular communication.
• Extracellular vesicles (EVs) are key mediators of this communication, carrying diverse molecular cargo.
• EVs' composition and diversity are significantly altered during cancer progression.

Purpose of the Study:

• To investigate how oncogenic transformation affects the molecular diversity and cargo of EVs.
• To explore the potential of single EV analysis in understanding cancer biology.
• To assess the diagnostic utility of EV profiling in cancer.

Main Methods:

• Analysis of EV proteome and molecular diversity using multicolour nano-flow cytometry and other single EV analysis platforms.
• Characterization of EV cargo alterations in response to oncogenic transformation, epithelial to mesenchymal transition, and cancer stem cell differentiation.
• Identification of specific EV populations, such as "oncosomes," carrying oncogenic proteins.

Main Results:

• Oncogenic transformation significantly alters the protein composition and diversity of EVs.
• EVs released from mutant cancer cells exhibit increased pro-invasive cargo.
• Distinct EV populations show altered composition due to transforming events.
• Single EV profiling reveals intricate changes in EV architecture.

Conclusions:

• Molecular profiling of single EVs provides deeper insights into the impact of cancer-driving events.
• Altered EV populations and cargo have significant implications for cancer biology.
• EVs hold promise as diagnostic and prognostic biomarkers in oncology.