| 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 pre-metastatic 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 pre-metastatic 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. |