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.

Synergies in exosomes and autophagy pathways for cellular homeostasis and metastasis of tumor cells.

BACKGROUND: Eukaryotic cells demonstrate two tightly linked vesicular transport systems, comprising intracellular vesicle transport and extracellular vesicle transport system. Intracellular transport vesicles can translocate biomolecules between compartments inside the cell, for example, proteins from the rough endoplasmic reticulum to the Golgi apparatus. Whereas, the secreted vesicles so-called extracellular vesicles facilitate the transport of biomolecules, for example, nucleic acids, proteins and lipids between cells. Vesicles can be formed during the process of endocytosis or/and autophagy and not only act as mediators of intra- and inter-cellular communication but also represent pathological conditions of cells or tissues. METHODS: In this review, we searched articles in PubMed, published between 2000 and 2020, with following terms: autophagy, autophagocytosis, transport vesicles, lysosomes, endosomes, exocytosis, exosomes, alone or in different combinations. The biological functions that were selected based on relevancy to our topic include cellular homeostasis and tumorigenesis. RESULTS: The searched literature shows that there is a high degree of synergies between exosome biogenesis and autophagy, which encompass endocytosis and endosomes, lysosomes, exocytosis and exosomes, autophagocytosis, autophagosomes and amphisomes. These transport systems not only maintain cellular homeostasis but also operate synergically against fluctuations in the external and internal environment such as during tumorigenesis and metastasis. Additionally, exosomal and autophagic proteins may serve as cancer diagnosis approaches. CONCLUSION: Exosomal and autophagy pathways play pivotal roles in homeostasis and metastasis of tumor cells. Understanding the crosstalk between endomembrane organelles and vesicular trafficking may expand our insight into cooperative functions of exosomal and autophagy pathways during disease progression and may help to develop effective therapies against lysosomal diseases including cancers and beyond.

Tumor-derived extracellular vesicles: insights into bystander effects of exosomes after irradiation.

This review article aims to address the kinetic of TDEs in cancer cells pre- and post-radiotherapy. Radiotherapy is traditionally used for the treatment of multiple cancer types; however, there is growing evidence to show that radiotherapy exerts NTEs on cells near to the irradiated cells. In tumor mass, irradiated cells can affect non-irradiated cells in different ways. Of note, exosomes are nano-scaled cell particles releasing from tumor cells and play key roles in survival, metastasis, and immunosuppression of tumor cells. Recent evidence indicated that irradiation has the potential to affect the dynamic of different signaling pathways such as exosome biogenesis. Indeed, exosomes act as intercellular mediators in various cell communication through transmitting bio-molecules. Due to their critical roles in cancer biology, exosomes are at the center of attention. TDEs contain an exclusive molecular signature that they may serve as tumor biomarker in the diagnosis of different cancers. Interestingly, radiotherapy and IR could also contribute to altering the dynamic of exosome secretion. Most probably, the content of exosomes in irradiated cells is different compared to exosomes originated from the non-irradiated BCs. Irradiated cells release exosomes with exclusive content that mediate NTEs in BCs. Considering variation in cell type, IR doses, and radio-resistance or radio-sensitivity of different cancers, there is, however, contradictions in the feature and activity of irradiated exosomes on neighboring cells.