Exosomes play roles in sequential processes of tumor metastasis

Abstract

Overwhelming evidence demonstrates that exosomes, a series of biologically functional small vesicles of endocytic origin carrying a variety of active constituents, especially tumor-derived exosomes, contribute to tumor progression and metastasis. This review focuses on the specific multifaceted roles of exosomes in affecting sequenced four crucial processes of metastasis, through which cancer cells spread from primary to secondary organs and finally form macroscopic metastatic lesions. First, exosomes modulate the primary tumor sites to assist cancer growth and dissemination. In this part, five main biological events are reviewed, including the transfer of oncogenic constituents, the recruitment and activation of fibroblasts, the induction of angiogenesis, immunosuppression and epithelial-mesenchymal transition (EMT) promotion. In Step 2, we list two recently disclosed mechanisms during the organ-specific homing process: the exosomal integrin model and exosomal epidermal growth factor receptor (EGFR)/miR-26/hepatocyte growth factor (HGF) model. Subsequently, Step 3 focuses on the interactions between exosomes and pre-metastatic niche, in which we highlight the specific functions of exosomes in angiogenesis, lymphangiogenesis, immune modulation and metabolic, epigenetic and stromal reprogramming of pre-metastatic niche. Finally, we summarize the mechanisms of exosomes in helping the metastatic circulating tumor cells escape from immunologic surveillance, survive in the blood circulation and proliferate in host organs.

Extracellular Vesicles from Hyperammonemic Rats Induce Neuroinflammation and Motor Incoordination in Control Rats

“…These reports, together with the present results, suggest that EVs may play a relevant role in the transmission of deleterious effects from peripheral blood to brain in different pathological situations, including hyperammonemia and MHE. There is overwhelming evidence that exosomes, a subtype of EVs, contribute to tumor progression and metastasis [49,50], to the immunopathology in infectious diseases [51] and to neurodegenerative diseases [52]. We show here that EVs also contribute to the induction of neuroinflammation and motor incoordination in hyperammonemia and likely MHE, in which motor incoordination is induced by similar mechanisms.…”

“…Peripheral EVs may also trigger neuroinflammation. Li et al [49] purified serum EVs from a mice model of endotoxemia with LPS and injected them to normal mice. They found that this induced microglial activation, astrogliosis, and increased expression of pro-inflammatory IL-6 and TNFα in hippocampus and cerebral cortex in recipient mice.…”

Exosomes promote pre-metastatic niche formation in ovarian cancer

“…Recent works have shown the pre-metastatic niche in ovarian cancer to be a prevalent precondition of metastasis [5]. The pre-metastatic niche is a preformed microenvironment made possible by exosomes secreted by the primary tumor site prior to widespread metastasis [6][7][8]. These exosomes optimize the environment for ovarian cancer colonization, outgrowth, and metastasis [9,10].…”

Complex N‐glycan promotes CD133 mono‐ubiquitination and secretion

“…Extracellular membrane trafficking via exosomes and other plasma membrane-derived vesicles can promote tumor growth and metastasis [50]. Many studies have demonstrated that CD133-containing vesicles are involved in a series of important biological processes such as cell differentiation, cancer progression, and extracellular cell communication [15][16][17].…”