Abstract
Seminal discoveries have established the role of complex tumor microenvironment (TME) in cancer progression; and later on also uncovered that vesiculation is an integral part of intercellular communication among various cell types in coordinating the tumor assembly in a dynamic manner. Exosomes are small membrane bound endosomal vesicles, which are classically known for their role in discarding cellular wastes; however, recent reports underlined their novel role in malignancy by their release from cells into the TME. Since then, the role of exosomes have been a subject of increasing interest, as exosome mediated intercellular communications offer a novel reciprocal relationship between cancer and stromal cells within the TME and modulate the fate and function of the recipient cells to finally shape the tumor progression. Exosomes are characterised by different features including size, content and mode of delivery; and its cargo delivers interesting bioactive components in the form of proteins, miRNAs or other molecules to the target cell. In the pursuit of further study of exosomes, it was found that with the help of its distinct bioactive components, exosomes specifically regulate tumor growth, angiogenesis, metastasis as well as drug resistance properties. In fact, it acts as a bridge between different signaling networks, present inside the spatially distant cells of the heterogeneous tumor population. In the current endeavour, we have highlighted the role of exosomes in modulating the intercellular crosstalk during tumor growth and progression, and proposed certain novel roles of exosomes to address the few enigmatic questions of cancer cell biology.
Highlights
Cell secretion is a widely accepted phenomenon and a fundamental process for the maintenance of physiological functions of a cell.[1]
In case of tumor development and progression, exosome has emerged as an important mediator of cellular communication and opened up a window that extends our understanding about how certain secretory vesicles perform a critical function of transferring genetic material, induce epigenetic changes, modulate immune response to manipulate the local and systemic tumor environment to regulate cancer growth and dissemination
In an in vitro study, it has been demonstrated that 786-0 renal cancer cell derived exosomes increased migration and invasion capacity of these cells by decreasing the adhesion ability and increasing the expression levels of CXCR4 and Matrix metalloproteinases (MMPs)-9.95 metastasis promoting epithelial-mesenchymal transition (EMT) related factors, such as vimentin, hepatoma-derived growth factor (HDGF) were found in the plasma membrane and annexin 2, CK2α, and moesin in the lumen of exosomes of bladder cancer respectively, suggesting their crucial involvement in metastatic process.[96]
Summary
Cell secretion is a widely accepted phenomenon and a fundamental process for the maintenance of physiological functions of a cell.[1]. The word ‘exosome’ was proposed for the first time for EV of endosomal origin in 1987.4-6 Exosomes are small lipid bilayer vesicles secreted by most but not all types of cells in their microenvironment. Besides their well known role in discarding waste material from the cells, exosomes play an important function in maintaining normal as well as pathological processes.[7] In case of tumor development and progression, exosome has emerged as an important mediator of cellular communication and opened up a window that extends our understanding about how certain secretory vesicles perform a critical function of transferring genetic material, induce epigenetic changes, modulate immune response to manipulate the local and systemic tumor environment to regulate cancer growth and dissemination. Current endeavour is an attempt to shed light on the emerging role of tumor-secreted exosomes as a novel player to modulate the tumor microenvironment during carcinogenesis
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