Biodistribution, Uptake and Effects Caused by Cancer-Derived Extracellular Vesicles

Abstract

Extracellular vesicles (EVs) have recently emerged as important mediators of intercellular communication. They are released in the extracellular space by a variety of normal and cancerous cell types and have been found in all human body fluids. Cancer-derived EVs have been shown to carry lipids, proteins, mRNAs, non-coding and structural RNAs and even extra-chromosomal DNA, which can be taken up by recipient cells and trigger diverse physiological and pathological responses. An increasing body of evidence suggests that cancer-derived EVs mediate paracrine signalling between cancer cells. This leads to the increased invasiveness, proliferation rate and chemoresistance, as well as the acquisition of the cancer stem cell phenotype. This stimulates angiogenesis and the reprogramming of normal stromal cells into cancer-promoting cell types. Furthermore, cancer-derived EVs contribute to the formation of the pre-metastatic niche and modulation of anti-tumour immune response. However, as most of these data are obtained by in vitro studies, it is not entirely clear which of these effects are recapitulated in vivo. In the current review, we summarize studies that assess the tissue distribution, trafficking, clearance and uptake of cancer-derived EVs in vivo and discuss the impact they have, both locally and systemically.

Methylation Markers in Cutaneous Melanoma: Unravelling the Potential Utility of Their Tracking by Liquid Biopsy

“…They play a key role in the delivery of active cargoes, including DNA fragments, coding and non-coding RNA, proteins, and lipids, from donor to distal cells, and they are released by normal and cancerous cells into the external microenvironment [ 177 ]. Tumor-derived EVs have been shown to affect the pathophysiology of recipient cells, modulating a variety of processes involved in cancer progression (increased invasiveness, proliferation rate, and chemoresistance) [ 178 ].…”

Nanoparticle-based biosensors for detection of extracellular vesicles in liquid biopsies

“…For instance, EVs released by highly aggressive, drug resistant or hypoxia-experienced cancer cells transfer their phenotypic traits to other cancer cells. [37][38][39] Cancer-derived EVs can also be taken up by various cell types constituting the tumor microenvironment leading to stromal activation, induction of angiogenesis, lymphangiogenesis and immune suppression. 40,41 Furthermore, cancer-derived EVs can act systemically by helping to establish pre-metastatic niches in lymph nodes and organ-specific distal sites.…”