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Review
. 2021 Jan;54(1):e12948.
doi: 10.1111/cpr.12948. Epub 2020 Nov 3.

Extracellular vesicle-associated organotropic metastasis

Zhenzhen Mo  1 , Jia Yang Alex Cheong  2 , Lirong Xiang  1 , Minh T N Le  3 , Andrew Grimson  4 , Daniel Xin Zhang  5   4
Affiliations
Review

Extracellular vesicle-associated organotropic metastasis

Zhenzhen Mo et al. Cell Prolif. 2021 Jan.

Abstract

Metastasis refers to the progressive dissemination of primary tumour cells and their colonization of other tissues and is associated with most cancer-related mortalities. The disproportional and systematic distribution pattern of distant metastasis in different cancers has been well documented, as is termed metastatic organotropism, a process orchestrated by a combination of anatomical, pathophysiological, genetic and biochemical factors. Extracellular vesicles (EVs), nanosized cell-derived membrane-bound particles known to mediate intercellular communication, are now considered crucial in organ-specific metastasis. Here, we review and summarize recent findings regarding EV-associated organotropic metastasis as well as some of the general mechanisms by which EVs contribute to this important process in cancer and provide a future perspective on this emerging topic. We highlight studies that demonstrate a role of tumour-derived EVs in organotropic metastasis via pre-metastatic niche modulation. The bioactive cargo carried by EVs is of diagnostic and prognostic values, and counteracting the functions of such EVs may be a novel therapeutic strategy targeting metastasis. Further investigations are warranted to better understand the functions and mechanisms of EVs in organotropic metastasis and accelerate the relevant clinical translation.

Keywords: cancer; exosomes; extracellular vesicles; metastasis; microvesicles; organotropism.

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Conflict of interest statement

MTNL is a cofounder, advisor and shareholder of Carmine Therapeutics, a red blood cell extracellular vesicle company. MTNL and AG are among the co‐inventors of the US provisional patent US 63/000,468 "Methods of delivering agents to immune cells". Other authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Extracellular vesicle (EV)‐mediated organotropic metastasis via pre‐metastatic niche modulation. Investigations showed that pre‐metastatic niche modulation via EVs plays a major role. Primary tumour cells disseminate EVs which can travel to distant metastatic sites and modulate resident or stroma cells in the pre‐metastatic microenvironment through various pathways, such as promotion of pro‐inflammatory gene expression and cytokine secretion, direction of phenotype‐specific induction/differentiation, and recruitment of specific cell types. The EV‐mediated modulation prepares a favourable pre‐metastatic niche at distance for metastatic tumour cells to reside in and grow
Figure 2
Figure 2
Stroma‐to‐tumour communication via EVs. Resident cells at metastatic sites can, in turn, secrete EVs for uptake by tumour cells and promote secondary tumour outgrowth. In this instance, astrocyte‐derived EVs containing microRNA‐19a can be internalized by metastatic tumour cells in brain, cause their downregulation of PTEN and promote the secretion of chemokine CCL2. CCL2 further recruits IBAB+ myeloid cells to facilitate the metastatic tumour outgrowth
Figure 3
Figure 3
Applications of organotropic metastasis‐associated EVs. These metastatic and organotropic aspects of tumour‐derived EVs can be of great diagnostic, prognostic, and therapeutic potentials and of emerging interests in biomedical and translational research
See this image and copyright information in PMC

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