OVERVIEW

Cell-membrane–derived vesicles are spherical membrane fragments shed by several cell types during their normal functioning. In the past, this “cellular dust” was overlooked and dismissed as insignificant debris. However, a role for these particles in physiological processes such as coagulation, immune regulation, intercellular crosstalk, and molecule delivery has now been established. In addition, increasing attention has been focused on the role of membrane vesicles in pathological processes, particularly as a cell–cell communication system that promotes tumorigenesis and malignant progression. This chapter outlines the complex interplay between membrane vesicles derived from tumor cells and host cells. Although molecular pathways involved in membrane vesicle biology and function have not been delineated, therapeutic manipulation of membrane-derived vesicles in patients with cancer has already entered the clinical arena. In the future, targeting membrane-derived vesicles may prove to be an effective approach in reducing morbidity and mortality of advanced malignancy, particularly in metastatic disease.

INTRODUCTION

Membrane-derived vesicles have been broadly classified into two types based on their size and mechanism of release. Microvesicles are small, heterogeneous membrane particles between 100 nm and 1 μm in size that are released from the intracellular endosome by membrane blebbing. In contrast, exosomes are even smaller membrane particles (30 nm–100 nm) thought to originate from multivesicular bodies during endocytosis. Although membrane vesicles derived from cells of hematopoietic origin were the first to be identified, including those released from B and T lymphocytes, platelets, dendritic cells, mast cells, and reticulocytes, recent evidence indicates that nonhematopoietic cell types, such as neurons, epithelial cells, and tumor cells, can also shed microvesicles.