Micromanaging of tumor metastasis by extracellular vesicles.

Extracellular vesicles (EVs) are nanometer-sized membranous vesicles that are released by a variety of cell types into the extracellular space. In the past two decades, EVs have emerged as novel mediators of cancer biology. Many reports have demonstrated the contribution of EVs to cancer metastasis. Metastasis is a multistep process that is responsible for the majority of deaths in cancer patients. This process includes proliferation, angiogenesis, immune modulation, extravasation, intravasation, and colonization. EVs from cancer cells impact these steps through modulation of the host immune system, angiogenesis, and pre-/pro-metastatic niche formation. In this review, we summarize the function of EVs in cancer metastasis. In addition, we also discuss the hurdles to be overcome for further developing this research field.

Tominaga N ，Katsuda T ，Ochiya T 《-》

Involvement of Extracellular Vesicles in Vascular-Related Functions in Cancer Progression and Metastasis.

Kikuchi S ，Yoshioka Y ，Prieto-Vila M ，Ochiya T ... -  《-》

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 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.

Rezaie J ，Ahmadi M ，Ravanbakhsh R ，Mojarad B ，Mahbubfam S ，Shaban SA ，Shadi K ，Berenjabad NJ ，Etemadi T ... -  《-》

The multifaceted role of extracellular vesicles in metastasis: Priming the soil for seeding.

Extracellular vesicles (EVs), including exosomes, play a key role in inter and intracellular communication, promoting the proliferation and invasion of recipient cells to support tumor growth and metastasis. Metastasis comprises multiple steps that first include the detachment of tumor cells through epithelial to mesenchymal transition (EMT), allowing the physical dissemination to distant organs. Thereafter, cancer-derived exosomes are still critical components for preparing the tumor microenvironment by (i) enabling tumor cells to escape from the immunological surveillance and (ii) arranging the pre-metastatic site for the engraftment of detached cancer cells. In this review, we discuss the multifaceted role of EVs in the multiple steps of metastasis. Future research directions draw attention to EVs as biological targets for cancer diagnosis, prognosis and therapy. However, due to their significant role in cell communication, they may become a valuable drug delivery system.

Dos Anjos Pultz B ，Andrés Cordero da Luz F ，Socorro Faria S ，Peixoto Ferreira de Souza L ，Cristina Brígido Tavares P ，Alonso Goulart V ，Fontes W ，Ricardo Goulart L ，José Barbosa Silva M ... -  《-》

Extracellular Vesicles in Cancer: Cell-to-Cell Mediators of Metastasis.

Tumor-secreted extracellular vesicles (EVs) are critical mediators of intercellular communication between tumor cells and stromal cells in local and distant microenvironments. Accordingly, EVs play an essential role in both primary tumor growth and metastatic evolution. EVs orchestrate multiple systemic pathophysiological processes, such as coagulation, vascular leakiness, and reprogramming of stromal recipient cells to support pre-metastatic niche formation and subsequent metastasis. Clinically, EVs may be biomarkers and novel therapeutic targets for cancer progression, particularly for predicting and preventing future metastatic development.

Becker A ，Thakur BK ，Weiss JM ，Kim HS ，Peinado H ，Lyden D ... -  《-》