Role of extracellular vesicles in tumour microenvironment

Abstract

In recent years, it has been demonstrated that extracellular vesicles (EVs) can be released by almost all cell types, and detected in most body fluids. In the tumour microenvironment (TME), EVs serve as a transport medium for lipids, proteins, and nucleic acids. EVs participate in various steps involved in the development and progression of malignant tumours by initiating or suppressing various signalling pathways in recipient cells. Although tumour-derived EVs (T-EVs) are known for orchestrating tumour progression via systemic pathways, EVs from non-malignant cells (nmEVs) also contribute substantially to malignant tumour development. Tumour cells and non-malignant cells typically communicate with each other, both determining the progress of the disease. In this review, we summarise the features of both T-EVs and nmEVs, tumour progression, metastasis, and EV-mediated chemoresistance in the TME. The physiological and pathological effects involved include but are not limited to angiogenesis, epithelial–mesenchymal transition (EMT), extracellular matrix (ECM) remodelling, and immune escape. We discuss potential future directions of the clinical application of EVs, including diagnosis (as non-invasive biomarkers via liquid biopsy) and therapeutic treatment. This may include disrupting EV biogenesis and function, thus utilising the features of EVs to repurpose them as a therapeutic tool in immunotherapy and drug delivery systems. We also discuss the overall findings of current studies, identify some outstanding issues requiring resolution, and propose some potential directions for future research.

Extracellular vesicles: Critical players during cell migration

“…Similarly, cell-cell communication and cell migration are integral parts of many disease processes. One notable example is cancer, where exosomes and other EVs have been shown to drive multiple aspects of cancer metastasis, including promotion of cancer cell motility and invasiveness and seeding of premeta-static niches (Sato and Weaver, 2018;Tao and Guo, 2020;Wortzel et al, 2019).…”

Perioperative Intravenous Lidocaine and Metastatic Cancer Recurrence - A Narrative Review

“…PMNs are pre-programmed by extracellular vesicles (EVs) released by the primary tumour - these are cell-derived, membranous structures containing proteins, lipids, messenger RNAs and microRNAs ( 21 , 22 ). MicroRNAs in particular are potent contributors to PMN formation, allowing malignancies to achieve remote ‘epigenetic regulation’ by altering gene expression in PMN cells to establish a pro-neoplastic milieu facilitating vascular permeability, angiogenesis and stromal degradation ( 5 , 23 , 24 ).…”

Bacterial Extracellular Vesicles in Gastrointestinal Tract Cancer: An Unexplored Territory

“…The TME is composed of a complex ecosystem containing diverse types of cells, including cancer cells, cancer-associated fibroblasts, endothelial cells, adipocytes, mesenchymal stem cells, immune cells such as macrophages, T cells, B cells, and infiltrated cytokines, as well as non-cellular components, such as micro vesicles, and the extracellular matrix as reviewed in [219][220][221][222]. Studies have indicated that the interaction between tumor cells, the neighboring cells, and immune cells moderates tumor growth, progression, and metastasis as reviewed in [223,224]. Studies carried out on tumor cell-derived EVs have shown that they play a significant role in regulating key signaling pathways to modulate the TME and, thus, tumor progression.…”