**1. Introduction**

Extracellular vesicles (EVs) are traditionally classified into three types: exosomes (Exo), microvesicles (MVs), and apoptotic vesicles. Several theories exist on how tumor cells alter their neighboring cells and matrix ultimately changing their behavior into an invasive one. This typically would involve the transport of materials from tumor cells to their adjacent surroundings. These materials include a wide range of soluble cytokines, RNA species, enzymes, and proteins. Most of which are carried in nano-sized carriers such as EVs. EVs are classified according to their size and the mechanism of genesis. The first class of EVs known as MVs or when secreted from cancer cells, are called oncosomes [1]. MVs formation is originated by the outward budding of the cell surface at specific regions along the plasma membrane enriched with high concentrations of lipids, such as cholesterol and glycosphingolipids, and proteins such as Flotillin-1 and 2 [2]. Exo represent the second major class of EVs [3]. They are formed when multivesicular bodies (MVBs) in the endo-lysosomal pathway accumulate intraluminal vesicles (ILVs) that consist of proteins and nucleic acids. Exo are smaller in size and range from 30 to 50 nm.

EVs can function in an autocrine, paracrine, and even endocrine fashion, and were shown to impact various cancer cell phenotypes, increasing their cell growth and promoting metastasis [4]. This secretome is released into the microenvironment and acts as cell-cell communicators. Tumor derived Exo (TDE) has appeared as imperative facilitators in cancer initiation, progression, metastasis, host immune suppression, and drug resistance [5]. TDE typically consists of high sphingolipids and cholesterol contents that contain major histocompatibility complex (MHC) molecules, heat shock proteins, and tetraspanin (CD63, CD81, and CD9). Additionally, tumor antigens such as Mart1, gp100, TRP, and Her2-neu have been discovered in TDE [5]. TDE also contains surface and soluble proteins and RNA species such as mRNAs and miRNAs. mRNAs conveyed in EVs result in proteins synthesis in target cells, while miRNAs alter their gene expression [6]. The *protein cargo* of TDE includes extracellular matrix (ECM) proteins, cell adhesion proteins, cell-surface receptor tyrosine kinases, chaperones, cytosolic and nuclear signaling proteins, as well as DNA and RNA binding proteins. Several types of nucleic acids that have been identified in EVs include RNA transcripts, microRNAs, long non-coding RNAs (lncRNAs), and DNA [7].
