The Role of Extracellular Vesicles in the Hallmarks of Cancer and Drug Resistance

Abstract

Extracellular vesicles (EVs) mediate intercellular signaling and communication, allowing the intercellular exchange of proteins, lipids, and genetic material. Their recognized role in the maintenance of the physiological balance and homeostasis seems to be severely disturbed throughout the carcinogenesis process. Indeed, the modus operandi of cancer implies the highjack of the EV signaling network to support tumor progression in many (if not all) human tumor malignancies. We have reviewed the current evidence for the role of EVs in affecting cancer hallmark traits by: (i) promoting cell proliferation and escape from apoptosis, (ii) sustaining angiogenesis, (iii) contributing to cancer cell invasion and metastasis, (iv) reprogramming energy metabolism, (v) transferring mutations, and (vi) modulating the tumor microenvironment (TME) by evading immune response and promoting inflammation. Special emphasis was given to the role of EVs in the transfer of drug resistant traits and to the EV cargo responsible for this transfer, both between cancer cells or between the microenvironment and tumor cells. Finally, we reviewed evidence for the increased release of EVs by drug resistant cells. A timely and comprehensive understanding of how tumor EVs facilitate tumor initiation, progression, metastasis and drug resistance is instrumental for the development of innovative EV-based therapeutic approaches for cancer.

Exosomes in Angiogenesis and Anti-angiogenic Therapy in Cancers

“…In addition, the vesicles participate in the biogenesis of lysosome-associated organelles in specialized cells and the transport of specific proteins to membranes, and are subject to degradation within lysosomes (IVLs derived from cholesterol-poor MVBs) [ 22 , 23 ]. Exosomes have been found in whole blood, plasma, cerebrospinal fluid, urine, semen, saliva, synovial fluid, milk, tears, nasal secretions and feces [ 24 , 25 , 26 , 27 ].…”

Extracellular Vesicles in the Development of Cancer Therapeutics

“…Cancer progression is a dysregulated and uncontrolled pathological process [ 52 ]. It is well described that cancer-derived sEVs promote tumor development [ 53 , 54 , 55 ] by acting at different stages of cancer progression [ 56 ] through various mechanisms. Evidence is provided to indicate that cancer sEVs are involved in enhancing tumorigenesis of epithelial cells [ 53 , 57 ], sustaining tumor angiogenesis [ 58 , 59 ], promoting tumor growth [ 60 , 61 ], facilitating cancer cell invasion and metastasis [ 54 , 55 , 62 , 63 ], and contributing to chemo-resistance [ 64 , 65 ] and immunosuppression [ 66 , 67 ].…”

Overexpression of sperm associated antigen 5 promotes cell growth, metastasis, and adriamycin resistance in esophageal squamous cell carcinoma via activating PI3K/AKT signaling pathway

“…Drug resistance of tumor cells is the main reason for the failure of clinical chemotherapy [21]. We found that SPAG5 was highly expressed not only in ESCC tumor tissues and cell lines, but also in adriamycin resistant ESCC cells ( Figure 7).…”

“…The proliferation, apoptosis, migration and invasion of tumor cells are the necessary stages of tumor occurrence and development [2,11,15,16,19]. Drug resistance is one of the important reasons for the low survival rate of cancer patients [21]. Our group plans to find potential therapeutic targets for esophageal cancer through bioinformatics analysis, clinical sample analysis, in vivo animal experiments and in vitro cell experiments.…”