Abstract
Intercellular communication is a normal feature of most physiological interactions between cells in healthy organisms. While cells communicate directly through intimate physiology contact, other mechanisms of communication exist, such as through the influence of soluble mediators such as growth factors, cytokines and chemokines. There is, however, yet another mechanism of intercellular communication that permits the exchange of information between cells through extracellular vesicles (EVs). EVs are microscopic (50 nm−10 μM) phospholipid bilayer enclosed entities produced by virtually all eukaryotic cells. EVs are abundant in the intracellular space and are present at a cells' normal microenvironment. Irrespective of the EV “donor” cell type, or the mechanism of EV biogenesis and production, or the size and EV composition, cancer cells have the potential to utilize EVs in a manner that enhances their survival. For example, cancer cell EV overproduction confers benefits to tumor growth, and tumor metastasis, compared with neighboring healthy cells. Herein, we summarize the current status of knowledge on different populations of EVs. We review the situations that regulate EV release, and the factors that instruct differential packaging or sorting of EV content. We then highlight the functions of cancer-cell derived EVs as they impact on cancer outcomes, promoting tumor progression, metastases, and the mechanisms by which they facilitate the creation of a pre-metastatic niche. The review finishes by focusing on the beneficial (and challenging) features of tumor-derived EVs that can be adapted and utilized for cancer treatments, including those already being investigated in human clinical trials.
Highlights
Several mechanisms of cell-to-cell and cell-to-microenvironment communication are used to maintain physiological processes in healthy organisms
extracellular vesicles (EV) play a role in tumor pathogenesis, starting from cancer initiation, propagation, formation of a pre-metastatic niche, and tumor migration, invasion and in cancer metastasis [7,8,9]
To see if monocytes taken from the blood of people with ovarian cancer can kill tumor cells
Summary
Several mechanisms of cell-to-cell and cell-to-microenvironment communication are used to maintain physiological processes in healthy organisms. The endosome as an organelle comprises internal membranes within the mammalian cell that fuses with the cells’ plasma membrane, forming multi-vesicular bodies (MVB) These are categorized as intraluminal vesicles (ILVs) when present in the cytoplasm, or as exosomes when released into the extracellular milieu. Different stimuli can change the production of EV types and vary cargo levels, or even post-transcriptional cargo modifications [67, 68] Factors such as the stimuli that triggers EV release, the donor cell type, and its normal physiological or disease condition, or the biogenesis pathway(s), influence the characteristics and abundance of the EVs present in human biological fluids, especially in situations of pathology including cancer. MICROVESICLES (MVs) Increasing intracellular Ca2+: 1. P2X7-R activation by ATP
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