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.

Intracellular and extracellular microRNA: An update on localization and biological role

“…Recent studies (reviewed in (Sadovska, 2015)) have demonstrated that after intravenous injection, the half-lives of EVs were only 2-5 min and already after 5-10 min EVs were found in the spleen, lung, liver, bone marrow, adipose tissue, and lymph nodes (Takahashi et al, 2013;Saunderson et al, 2014;Bala et al, 2015;Wiklander et al, 2015). Thus, those organs may accumulate EV after injection into the blood stream and, besides, a significant portion of EV could be absorbed by the macrophages present in those organs (Saunderson et al, 2014;Imai et al, 2015).…”

Circulating Cell-Free DNA in Breast Cancer: Searching for Hidden Information towards Precision Medicine

“…It has been demonstrated that EVs participate in the carcinogenic process and metastasis initiation, having a role in intracellular communication and transfection of healthy cells [ 151 , 152 ]. Tumor derived vesicles also contain single-strand DNA reflecting the genetic status of tumor cells [ 153 ], holding some value as a potent source of liquid biopsy.…”

Radiolabeling of Extracellular Vesicles with 99mTc for Quantitative In Vivo Imaging Studies

“…The in vivo fate of EVs has only been addressed in the last few years, and most studies used fluorescent imaging for this purpose. [11][12][13][14][15][16][17][18] In these studies EVs were either labeled with a membrane dye 13,18 or engineered to display a membrane reporter (e.g. Gaussia luciferase), and administered exogenously 15 or utilized endogenously produced, genetically modified EVs (such as GFP-tagged CD63 bearing EVs) 19 .…”