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RESEARCH PRODUCT

Transmission of Information in Neoplasia by Extracellular Vesicles.

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Paracrine interactions among neoplastic and nonneoplastic cells in the immediate tumor microenvironment are important for tumor growth and metastatic spreading. Most of the studies in the past decade addressing these cellular interactions have focused on tumor cell-derived soluble molecules. Recently, these studies and interest have shifted to nanosized extracellular vesicles (EVs) and especially ectosome and exosome-associated molecules [1]. They contain not only proteins, but also lipids, mRNA, and microRNA [1], which can regulate gene expression in their target cells in a much more pleiotropic manner [1]. While exosomes originate by a sequential process of inward budding of late endosomes, producing multivesicular bodies (MVBs), followed by release of internal microvesicles into the microenvironment by fusion of the MVBs with the plasma membrane [1, 2], ectosomes bud from plasma membrane, particularly from plasma membrane protrusions (e.g., microvilli) [1]. However, difficulties in obtaining homogeneous exosomal and ectosomal preparations result in incomplete understanding of their formation, composition, and functions [3]. Trafficking of biological materials across cellular membranes is part of any normal cell homeostasis, to maintain proper compartmentalization of important molecules. The physiological functions of EVs are extremely diverse (e.g., cell-cell communication, cellular differentiation, immunity, and inflammation) [4–8]. However, in pathological states, such as cancer, aberrant activity of the export machinery results in expulsion of a number of key proteins and microRNA that modify the tumor microenvironment, in turn stimulating the release of EVs from stromal and immune-competent cells. In cancers, such vehicles might play a role in carcinogenesis and disease progression and promote formation of the premetastatic niche [9–11]. In the present special issue on transmission of information in neoplasia by extracellular vesicles, review articles and research paper illustrate the relevance of EVs to cancer growth and metastasis.