Abstract
Extracellular vesicles (EVs) like exosomes and shed microvesicles are generated by many different cells. However, among all the cells, cancer cells are now recognized to secrete more EVs than healthy cells. Tumor-derived EVs can be isolated from biofluids such as blood, urine, ascitic fluid, and saliva. Their numerous components (nucleic acids, proteins, and lipids) possess many pleiotropic functions involved in cancer progression. The tumor-derived EVs generated under the influence of tumor microenvironment play distant roles and promote cellular communication by directly interacting with different cells. Moreover, they modulate extracellular matrix remodeling and tumor progression. Tumor-derived EVs are involved in pre-metastatic niche formation, dependent on the EV-associated protein receptors, and in cancer chemoresistance as they transfer drug-resistance-related genes to recipient cells. Recent advances in preclinical and clinical fields suggest their potential use as biomarkers for diagnosis and prognosis as well as for drug delivery in cancer. In this Review, we discuss EV characteristics and pro-tumor capacities, and highlight the future crucial impact of tumor-derived EVs in pancreatic cancer diagnosis and prognosis.
Highlights
Intercellular communication is essential to cell development and maintenance of homeostasis in multicellular organisms
Independent pathways have been shown to be involved in Extracellular vesicles (EVs) biogenesis: the endosomal sorting complex required for the transport (ESCRT) dependent pathway, the asymmetry lipid involvement required for the budding formation and release, the tetraspanin-dependent pathway responsible for selecting cargoes for exosomes, the syndecan and syntenin pathways required for budding [2, 26,27,28]
KRAS mutation allele frequency (MAF) from exosomal DNA is significantly associated with disease progression after neoadjuvant chemotherapy in a prospective cohort of potentially resectable pancreatic tumor
Summary
Intercellular communication is essential to cell development and maintenance of homeostasis in multicellular organisms. Produced and released into the extracellular microenvironment by most cell types and belonging multiple distinct classes depending on their origin, EVs are predominantly described in intercellular communication their functions are not limited to this aspect [1]. These cell-to-cell communications occur locally or at distance. Numerous studies have shown the biological roles of EVs in physio-pathological processes, such as immune and microbiological regulation, stem cell biology, cardiovascular diseases, Extracellular Vesicle in Pancreatic Cancer neurodegenerative diseases, metabolic disorders, and cancer progression [10,11,12,13]. The MISEV2018 guideline harmonizes these aspects and avoids misunderstandings such as the presence of potential contaminant in EV preparations [21]
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