TransNetwork Project 1

Comparative Studies of Exosomes and Microvesicles in Cancer Cell Biology

Project Investigator: Rick Cerione (Cornell University)

Collaborator: W. Guo (University of Pennsylvania)

The ultimate goal of these studies is to examine how the physical microenvironment of cancer cells affects the biogenesis and function of non-classical secretory vesicles, referred to as extracellular vesicles (EVs).  These vesicles have been implicated in a number of aspects of tumorigenesis and metastasis, including their roles in helping to shape the tumor microenvironment, as well as in the inability of immune cells to recognize and attack tumor cells, and in the development of the pre-metastatic niche at secondary sites of tumor colony formation.  There are two general classes of EVs that can be distinguished based on their sizes and the mechanisms underlying their biogenesis.  These are exosomes (which are typically <100 nm in diameter) that are formed by endosomal recycling and through multi-vesicular bodies, and microvesicles (200 nm-2 microns in diameter) that are exclusively formed and shed from the plasma membrane.  The purpose of these studies is to take advantage of the complementary expertise of the Cornell and Penn groups to determine how the physical microenvrionemnt influences the biogenesis of each of the two classes of EVs and to establish how these different vesicles, individually and in combination, influences the metastatic process and the ability of cancer cells to evade the immune system.