Probing the mechanisms of extracellular vesicle biogenesis and function in cancer.

Tumor cells interact with each other, and their surroundings, using a variety of mechanisms to promote virtually all aspects of cancer progression. One such form of intercellular communication that has been attracting considerable attention from the cancer community and the pharmaceutical industry in recent years involves the ability of cancer cells to generate multiple distinct types of non-classical secretory vesicles, generally referred to as extracellular vesicles (EVs). Microvesicles (MVs) represent one of the major classes of EVs and are formed as a result of the outward budding and fission of the plasma membrane. The other main class of EVs is exosomes, which are generated when multivesicular bodies fuse with the cell surface and release their contents into the extracellular space. Both MVs and exosomes have been shown to contain bioactive cargo, including proteins, metabolites, RNA transcripts, microRNAs, and DNA that can be transferred to other cancer cells and stimulate their growth, survival, and migration. However, cancer cell-derived EVs also play important roles in helping re-shape the tumor microenvironment to support tumor expansion and invasive activity, dampen immune responses, as well as enter the circulation to help promote metastatic spread. Here, we provide an overview of what is currently known regarding how the different classes of EVs are generated and contribute to various cancer cell phenotypes. Moreover, we highlight how some of the unique properties of EVs are being used for the development of novel diagnostic and clinical applications.

Latifkar A ，Cerione RA ，Antonyak MA 《-》

Extracellular Vesicles and Their Roles in Cancer Progression.

Chang WH ，Cerione RA ，Antonyak MA 《-》

New insights into extracellular vesicle biogenesis and function.

It is becoming increasingly evident that most cell types are capable of forming and releasing multiple distinct classes of membrane-enclosed packages, referred to as extracellular vesicles (EVs), as a form of intercellular communication. Microvesicles (MVs) represent one of the major classes of EVs and are formed by the outward budding of the plasma membrane. The second major class of EVs, exosomes, are produced as components of multivesicular bodies (MVBs) and are released from cells when MVBs fuse with the cell surface. Both MVs and exosomes have been shown to contain proteins, RNA transcripts, microRNAs and even DNA that can be transferred to other cells and thereby trigger a broad range of cellular activities and biological responses. However, EV biogenesis is also frequently de-regulated in different pathologies, especially cancer, where MVs and exosomes have been suggested to promote tumor cell growth, therapy resistance, invasion and even metastasis. In this Review, we highlight some of the recent advances in this rapidly emerging and exciting field of cell biology, focusing on the underlying mechanisms that drive MV and exosome formation and release, with a particular emphasis on how EVs potentially impact different aspects of cancer progression and stem cell biology.

Latifkar A ，Hur YH ，Sanchez JC ，Cerione RA ，Antonyak MA ... -  《-》

Extracellular vesicles and their roles in stem cell biology.

Stem cells use a variety of mechanisms to help maintain their pluripotency and promote self-renewal, as well as, at the appropriate time, to differentiate into specialized cells. One such mechanism that is attracting significant attention from the stem cell, development, and regenerative medicine research communities involves a form of intercellular communication, specifically, the ability of cells to form and release nontraditional membrane-enclosed structures, referred to as extracellular vesicles (EVs). There are two major classes of EVs, microvesicles (MVs), which are generated through the outward budding and fission of the plasma membrane, and exosomes, which are formed as multivesicular bodies (MVBs) in the endo-lysosomal pathway that fuse with the cell surface to release their contents. Although they differ in how they are formed, both MVs and exosomes have been shown to contain a diverse array of bioactive cargo, such as proteins, RNA transcripts, microRNAs, and even DNA, which can be transferred to other cells and promote phenotypic changes. Here, we will describe what is currently known regarding EVs and the roles they play in stem cell biology and different aspects of early development. We will also highlight how the EVs produced by stem cells are being aggressively pursued for clinical applications, including their potential use as therapeutic delivery systems and for their regenerative capabilities.

Hur YH ，Cerione RA ，Antonyak MA 《-》

Focus on Extracellular Vesicles: New Frontiers of Cell-to-Cell Communication in Cancer.

Ciardiello C ，Cavallini L ，Spinelli C ，Yang J ，Reis-Sobreiro M ，de Candia P ，Minciacchi VR ，Di Vizio D ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》