Extracellular Vesicles and Cancer: A Focus on Metabolism, Cytokines, and Immunity

Abstract

A better understanding of the mechanisms of cell communication between cancer cells and the tumor microenvironment is crucial to develop personalized therapies. It has been known for a while that cancer cells are metabolically distinct from other non-transformed cells. This metabolic phenotype is not peculiar to cancer cells but reflects the characteristics of the tumor microenvironment. Recently, it has been shown that extracellular vesicles are involved in the metabolic switch occurring in cancer and tumor-stroma cells. Moreover, in an immune system, the metabolic programs of different cell subsets are distinctly associated with their immunological function, and extracellular vesicles could be a key factor in the shift of cell fate modulating cancer immunity. Indeed, during tumor progression, tumor-associated immune cells and fibroblasts acquire a tumor-supportive and anti-inflammatory phenotype due to their interaction with tumor cells and several findings suggest a role of extracellular vesicles in this phenomenon. This review aims to collect all the available evidence so far obtained on the role of extracellular vesicles in the modulation of cell metabolism and immunity. Moreover, we discuss the possibility for extracellular vesicles of being involved in drug resistance mechanisms, cancer progression and metastasis by inducing immune-metabolic effects on surrounding cells.

The Wnt Signalling Pathway: A Tailored Target in Cancer

“…Furthermore, since EVs are released within the TME, their contribution in cancer growth and progression has been extensively investigated [ 144 ]. EV shedding, blockade, or engineering have been proposed as innovative anti-tumour instruments for fine-tuning the Wnt/β catenin pathway [ 142 , 145 ].…”

Could Protons and Carbon Ions Be the Silver Bullets Against Pancreatic Cancer?

“…Growing evidence has brought the implication of extracellular microvesicles (EVs) as factors in chemo- and radioresistance of cancer cells [ 104 , 105 , 106 , 107 ]. EVs are microparticles with a lipid bilayer membrane, secreted from all cell types either in physiological and pathological conditions [ 81 ].…”

Anti-Inflammatory Potential of Cow, Donkey and Goat Milk Extracellular Vesicles as Revealed by Metabolomic Profile

“…Among them, high specificity for the target, great stability and ability to cross biological barriers are well documented [ 7 ]. EVs of different origins can induce many various responses in the target tissue, for example, enhancing tissue regeneration [ 8 , 9 ] or participating in immune modulation and modification of inflammatory conditions [ 10 , 11 , 12 , 13 ] and could represent a future alternative to stem cell therapies in some fields [ 14 , 15 ].…”

“…The entire metabolites content of EVs that is constituted by organic acids, amino acids, sugars and their conjugates, nucleotides and nucleosides, cyclic alcohols, carnitines, aromatic compounds and vitamins have been described, often focusing on a possible role of metabolites as cancer biomarkers from urine and blood [ 44 , 45 ]. At the best of our knowledge, there are no studies on MEV metabolites as immunomodulators and anti-inflammatories, while these properties have been observed in EVs [ 11 ].…”