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Characteristics, Events, and Stages in Tumorigenesis
Published in Franklyn De Silva, Jane Alcorn, The Elusive Road Towards Effective Cancer Prevention and Treatment, 2023
Franklyn De Silva, Jane Alcorn
Tumor-derived extracellular vesicles (TEVs) released from cancer cell types serve to orchestrate fundamental processes involved in tumorigenesis [840]. Inward budding within the endosomal/lysosomal pathway along with the fusion of multivesicular bodies (MVBs) with the plasma membrane gives rise to TEVs [840]. A series of complex molecular machinery orchestrates various processes of biogenesis, including MVBs/intraluminal vesicle (ILV) biogenesis, cargo sorting, membrane invagination, and the release of exosomes, respectively [840]. Some of the identified molecules involved in these machineries are the small Rab GTPase family (e.g., Rab11, Rab27, and Rab35), endosomal sorting complex required for transport (ESCRT -0, -I, -II, and -III), ceramide-generating sphingomyelinase, vacuolar protein-sorting 4 homolog A (VPS4A), accessory proteins (Alix, and VTA-1), tetraspanin-mediated organization of specific proteins (amyloidogenic protein premelanosome protein (PMEL)), ceramide synthesis to induce vesicle curvature and budding, and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) system [828, 830, 831, 840, 855, 896, 899, 902–915]. In addition, the amount of cholesterol or enrichment of lysobisphosphatidic acid and intracellular calcium changes are also believed to be involved in this regulation process [830, 840, 849, 916]. ‘Apoptotic bodies', a term coined by Kerr in 1972, are large EVs with a broad diameter shed by the plasma membrane of apoptotic cells containing mostly fragmented subcellular organelles for degradation, and they are picked up by phagocytic cells for digestion [851, 857, 898, 900, 917–920]. Therefore, these EVs are not involved in intercellular communication [857].
An updated review on exosomes: biosynthesis to clinical applications
Published in Journal of Drug Targeting, 2021
Sheela Modani, Devendrasingh Tomar, Suma Tangirala, Anitha Sriram, Neelesh Kumar Mehra, Rahul Kumar, Dharmendra Kumar Khatri, Pankaj Kumar Singh
In the process of exosomes uptake, exosomes pass the signals to the receiver cell, which involves a three-step mechanism [53]. First, exosomes identify the specific target cell and interact with receptors present on the cell membrane, then exosomes fuse to the membrane of the target cell and followed by the entry of the exosomes in the cell by endocytosis/phagocytosis mechanism. The phagocytosis of exosomes was shown to be dependent on the actin cytoskeleton, phosphatidylinositol 3-kinase (PI3K) and dynamin2. Notably, actin, PI3K and dynamin2 have all been implicated in both clathrin-mediated endocytosis and phagocytosis. Internalised exosomes co-localised with Lamp-1, lysobisphosphatidic acid and Rab7 in late autophagosomes and/or endosomal and lysosomal vesicles [53]. Clathrin-mediated endocytosis utilises clathrin and adaptor protein 2 complexes which coat the membrane and induce the invagination of the membrane into a vesicle [54]. Many reports in the literature also suggested internalisation as the most common mechanism of exosomes uptake, which is mainly dependent upon cell type and proteins present on cell membrane [55]. Uptake of exosomes by a recipient cell is specifically cell-specific, involving the interaction of proteins present on the surface of target cells and exosomes are crucial for recipient cell adhesion and targeting [56].