Exosome Secretion in Tumor Aggressiveness

PROJECT SUMMARY Exosomes are a type of small extracellular vesicle (EV) secreted from all kinds of cells, derived from endosomes. They have many physiological and pathological functions, such as cell proliferation and differentiation, angiogenesis and wound healing, regulation of immunity, and cancer progression. They also play roles in maintaining tumor microenvironments and driving cancer metastasis through cargo delivery to recipient cells in paracrine and autocrine manners. The laboratory of Dr. Alissa Weaver (Unit Director) at Vanderbilt University School of Medicine studies the regulation of cancer cell migration and invasion by exosomes and the role of cancer cell exosomes in cancer aggressiveness and metastasis. The lab also carries out research on the biogenesis of RNA-containing exosomes and the development of imaging tools to track exosomes. The proposed studies for this R50 application of Dr. Bong Hwan Sung (Research Specialist) are related to two NCI-funded R01 grants: 1. Exosome secretion in breast cancer progression. This project tests the central hypothesis that adhesion molecules carried by cancer and fibroblast exosomes drive multiple steps of the metastatic cascade in breast cancer. 2. Regulation of extracellular vesicle biogenesis through cell adhesion. This project tests the hypothesis that the biogenesis of motility-promoting EVs in cancer is controlled by syntenin-dependent regulation of EV formation and cargo loading downstream of activated leukocyte cell adhesion molecule (ALCAM)-mediated adhesions. Dr. Sung has worked with Dr. Weaver for the past 15 years. As an expert in cell biology, EVs, and imaging techniques, Dr. Sung has set up state-of-the-art imaging techniques, and developed experimental and imaging tools and image analysis methods in her laboratory. This project will support those ongoing efforts.