Tumor-derived extracellular vesicles: The metastatic organotropism drivers

The continuous growing, spreading, and metastasis of tumor cells depend on intercellular communication within
cells resident in a tissue environment. Such communication is mediated through the secretion of particles from
tumor cells and resident cells known as extracellular vesicles (EVs) within a microenvironment. EVs are a heterogeneous
population of membranous vesicles released from tumor cells that transfer many types of active
biomolecules to recipient cells and induce physiologic and phenotypic alterations in the tissue environment.
Spreading the ‘seeds’ of metastasis needs the EVs that qualify the ‘soil’ at distant sites to promote the progress of
arriving tumor cells. Growing evidence indicates that EVs have vital roles in tumorigenesis, including premetastatic
niche formation and organotropic metastasis. These EVs mediate organotropic metastasis by modifying
the pre-metastatic microenvironment through different pathways including induction of phenotypic
alternation and differentiation of cells, enrolment of distinct supportive stromal cells, up-regulation of the
expression of pro-inflammatory genes, and induction of immunosuppressive status. However, instead of premetastatic
niche formation, evidence suggests that EVs may mediate reawakening of dormant niches. Findings
regarding EVs function in tumor metastasis have led to growing interests in the interdisciplinary significance of
EVs, including targeted therapy, cell-free therapy, drug-delivery system, and diagnostic biomarker. In this review,
we discuss EVs-mediated pre-metastatic niche formation and organotropic metastasis in visceral such as
lung, liver, brain, lymph node, and bone with a focus on associated signaling, causing visceral environment
hospitable for metastatic cells. Furthermore, we present an overview of the possible therapeutic application of
EVs in cancer management.