Abstract
We have previously demonstrated that tumor cells release membranous structures into their extracellular environment, which are termed exosomes, microvesicles or extracellular vesicles depending on specific characteristics, including size, composition and biogenesis pathway. These cell-derived vesicles can exhibit an array of proteins, lipids and nucleic acids derived from the originating tumor. This review focuses of the transcriptome (RNA) of these extracellular vesicles. Based on current data, these vesicular components play essential roles as conveyers of intercellular communication and mediators of many of the pathological conditions associated with cancer development, progression and therapeutic failures. These extracellular vesicles express components responsible for angiogenesis promotion, stromal remodeling, signal pathway activation through growth factor/receptor transfer, chemoresistance, and genetic exchange. These tumor-derived extracellular vesicles not only to represent a central mediator of the tumor microenvironment, but their presence in the peripheral circulation may serve as a surrogate for tumor biopsies, enabling real-time diagnosis and disease monitoring.
Highlights
The release of 50–200 nm sized membranous vesicles into biological fluids by viable tumor cells was initially described by us over three decades ago (Taylor and Doellgast, 1979) and has since been demonstrated multiple cell types and systems
Three primary mechanisms have been proposed for the release of cellular components into the extracellular space: (1) exocytic fusion of multivesicular bodies (MVBs) resulting in “exosomes,” (2) budding of vesicles directly from the plasma membranes resulting in shed “microvesicles” and (3) cell death leading to apoptotic bodies
One issue for the use of extracellular vesicles as diagnostic markers is that they are released by other cells associated with the peripheral blood, including lymphocytes, platelets, and endothelial cells. This has established the need for isolation of specific vesicles populations, To address this, in our initial study, extracellular vesicles of tumor origin were isolated from the blood of women with ovarian cancer using antibodies reactive with epithelial cell adhesion molecule (EpCAM)
Summary
The release of 50–200 nm sized membranous vesicles into biological fluids by viable tumor cells was initially described by us over three decades ago (Taylor and Doellgast, 1979) and has since been demonstrated multiple cell types and systems. It may not be possible to differentiate 50–100 nm “exosomes” from 50 to 200 nm “microvesicles.” In many studies, uncharacterized cell-derived vesicles (in terms of markers or size) are termed “microvesicles,” while numerous studies define “exosomes” solely based on density and the presence of the cell surface markers, tetraspanins These overlaps in vesicle properties and terms suggest these distinctions may not be clear-cut. The in vivo appearance of tumor-derived vesicles within the circulation was initially demonstrated in ovarian cancer patients (Taylor and Doellgast, 1979; Taylor et al, 1980, 1983) These gynecologic cancer patients exhibited intact extracellular vesicles within their peripheral circulation and malignant effusions (ascites and cyst fluids). Extracellular vesicles have since been demonstrated to be released by a variety of non-cancerous cells, cells of the immune system, including dendritic cells, macrophages, www.frontiersin.org
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