scholarly journals Distinct Cargos of Small Extracellular Vesicles Derived from Hypoxic Cells and Their Effect on Cancer Cells

2020 ◽  
Vol 21 (14) ◽  
pp. 5071
Author(s):  
Geoffroy Walbrecq ◽  
Christiane Margue ◽  
Iris Behrmann ◽  
Stephanie Kreis
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Solid Tumors ◽  
Extracellular Vesicles ◽  
Biological Effects ◽  
Biological Molecules ◽  
Distant Future ◽  
Poor Outcome ◽  
Metastatic Sites

Hypoxia is a common hallmark of solid tumors and is associated with aggressiveness, metastasis and poor outcome. Cancer cells under hypoxia undergo changes in metabolism and there is an intense crosstalk between cancer cells and cells from the tumor microenvironment. This crosstalk is facilitated by small extracellular vesicles (sEVs; diameter between 30 and 200 nm), including exosomes and microvesicles, which carry a cargo of proteins, mRNA, ncRNA and other biological molecules. Hypoxia is known to increase secretion of sEVs and has an impact on the composition of the cargo. This sEV-mediated crosstalk ultimately leads to various biological effects in the proximal tumor microenvironment but also at distant, future metastatic sites. In this review, we discuss the changes induced by hypoxia on sEV secretion and their cargo as well as their effects on the behavior and metabolism of cancer cells, the tumor microenvironment and metastatic events.

scholarly journals Gastric Cancer Extracellular Vesicles Tune the Migration and Invasion of Epithelial and Mesenchymal Cells in a Histotype-Dependent Manner

2019 ◽  
Vol 20 (11) ◽  
pp. 2608 ◽  
Author(s):  
Sara Rocha ◽  
Sara Pinto Teles ◽  
Mafalda Azevedo ◽  
Patrícia Oliveira ◽  
Joana Carvalho ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Flow Cytometry ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Mesenchymal Cells ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Diffuse Type ◽  
Transmission Electron

Extracellular vesicles (EVs) secreted by tumor cells modulate recipient cells’ behavior, but their effects in normal cells from the tumor microenvironment remain poorly known. In this study, we dissected the functional impact of gastric cancer cell-derived EVs (GC-EVs), representative of distinct GC histotypes, on the behavior of normal isogenic epithelial and mesenchymal cells. GC-EVs were isolated by differential centrifugation and characterized by transmission electron microscopy, nanoparticle tracking analysis, and imaging flow-cytometry. Epithelial and mesenchymal cells were challenged with GC-EVs and submitted to proliferation, migration, and invasion assays. Expression of epithelial and mesenchymal markers was followed by immunofluorescence and flow-cytometry. Our results indicated that GC-EVs secreted by diffuse-type cancer cells decrease the migration of recipient cells. This effect was more prominent and persistent for mesenchymal recipient cells, which also increased Fibronectin expression in response to EVs. GC-EVs secreted by cancer cells derived from tumors with an intestinal component increased invasion of recipient epithelial cells, without changes in EMT markers. In summary, this study demonstrated that GC-EVs modulate the migration and invasion of epithelial and mesenchymal cells from the tumor microenvironment, in a histotype-dependent manner, highlighting new features of intestinal and diffuse-type GC cells, which may help explaining differential metastasis patterns and aggressiveness of GC histotypes.

scholarly journals Role of Exosomal miRNAs and the Tumor Microenvironment in Drug Resistance

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1450 ◽  
Author(s):  
Patrick Santos ◽  
Fausto Almeida
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Therapy Resistance ◽  
Chemotherapeutic Agents ◽  
Exosomal Mirnas ◽  
Key Factor

Tumor microenvironment (TME) is composed of different cellular populations, such as stromal, immune, endothelial, and cancer stem cells. TME represents a key factor for tumor heterogeneity maintenance, tumor progression, and drug resistance. The transport of molecules via extracellular vesicles emerged as a key messenger in intercellular communication in the TME. Exosomes are small double-layered lipid extracellular vesicles that can carry a variety of molecules, including proteins, lipids, and nucleic acids. Exosomal miRNA released by cancer cells can mediate phenotypical changes in the cells of TME to promote tumor growth and therapy resistance, for example, fibroblast- and macrophages-induced differentiation. Cancer stem cells can transfer and enhance drug resistance in neighboring sensitive cancer cells by releasing exosomal miRNAs that target antiapoptotic and immune-suppressive pathways. Exosomes induce drug resistance by carrying ABC transporters, which export chemotherapeutic agents out of the recipient cells, thereby reducing the drug concentration to suboptimal levels. Exosome biogenesis inhibitors represent a promising adjunct therapeutic approach in cancer therapy to avoid the acquisition of a resistant phenotype. In conclusion, exosomal miRNAs play a crucial role in the TME to confer drug resistance and survivability to tumor cells, and we also highlight the need for further investigations in this promising field.

Role of the Immune Component of Tumor Microenvironment in the Efficiency of Cancer Treatment: Perspectives for the Personalized Therapy

2017 ◽  
Vol 23 (32) ◽  
pp. 4807-4826 ◽  
Author(s):  
Marina Stakheyeva ◽  
Vladimir Riabov ◽  
Irina Mitrofanova ◽  
Nikolai Litviakov ◽  
Evgeny Choynzonov ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Solid Tumors ◽  
Immune Cells ◽  
Critical Factor ◽  
Cancer Diagnostics ◽  
Patient Specific ◽  
Intratumor Heterogeneity ◽  
Therapeutic Approaches

Despite significant progress in cancer diagnostics and development of novel therapeutic regimens, successful treatment of advanced forms of cancer is still a challenge and may require personalized therapeutic approaches. In this review, we analyzed major mechanisms responsible for tumor cells chemoresistance and emphasized that intratumor heterogeneity is a critical factor that limits efficiency of cancer treatment. Intratumor heterogeneity is caused by genomic instability in cancer cells, resulting in the selection of resistant clones. Moreover, cancer cells in solid tumors are surrounded by cellular and molecular microenvironment that actively influences tumor cell behavior. Local tumor microenvironment (TME) consisting of immune cells with diverse phenotypes and functions strongly contributes to intratumor heterogeneity and modulates responses to treatment. Thus, targeting specific components of TME is a novel treatment strategy that can improve the outcome of conventional anti-cancer therapy. Here, we discuss modern immunotherapeutic approaches based on targeting tumorinfiltrating immune cells including neutrophils, dendritic cells, NK cells, T cells, B cells and macrophages. Among those, tumor-associated macrophages (TAM) that display a pronounced heterogeneity and phenotypic plasticity appear to be a major component in the TME of solid tumors, and emerge as perspective targets for cancer immunotherapy. TAM intratumor heterogeneity and the possible existence of patient-specific phenotype signature generate the basis for the development of individualized TAM-based therapeutic approaches.

scholarly journals Exploiting Manipulated Small Extracellular Vesicles to Subvert Immunosuppression at the Tumor Microenvironment through Mannose Receptor/CD206 Targeting

2020 ◽  
Vol 21 (17) ◽  
pp. 6318 ◽  
Author(s):  
Maria Luisa Fiani ◽  
Valeria Barreca ◽  
Massimo Sargiacomo ◽  
Flavia Ferrantelli ◽  
Francesco Manfredi ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Solid Tumors ◽  
Extracellular Vesicles ◽  
Biochemical Characterization ◽  
Critical Role ◽  
Tumor Development ◽  
Cell Communication ◽  
Mannose Receptor ◽  
Therapeutic Molecules ◽  
Ideal Tool

Immunosuppression at tumor microenvironment (TME) is one of the major obstacles to be overcome for an effective therapeutic intervention against solid tumors. Tumor-associated macrophages (TAMs) comprise a sub-population that plays multiple pro-tumoral roles in tumor development including general immunosuppression, which can be identified in terms of high expression of mannose receptor (MR or CD206). Immunosuppressive TAMs, like other macrophage sub-populations, display functional plasticity that allows them to be re-programmed to inflammatory macrophages. In order to mitigate immunosuppression at the TME, several efforts are ongoing to effectively re-educate pro-tumoral TAMs. Extracellular vesicles (EVs), released by both normal and tumor cells types, are emerging as key mediators of the cell to cell communication and have been shown to have a role in the modulation of immune responses in the TME. Recent studies demonstrated the enrichment of high mannose glycans on the surface of small EVs (sEVs), a subtype of EVs of endosomal origin of 30–150 nm in diameter. This characteristic renders sEVs an ideal tool for the delivery of therapeutic molecules into MR/CD206-expressing TAMs. In this review, we report the most recent literature data highlighting the critical role of TAMs in tumor development, as well as the experimental evidences that has emerged from the biochemical characterization of sEV membranes. In addition, we propose an original way to target immunosuppressive TAMs at the TME by endogenously engineered sEVs for a new therapeutic approach against solid tumors.

Effects of Exosomes on Major Pathways Promote Tumor Formation and Progression

2021 ◽  
Vol 21 ◽  
Author(s):  
Mehmet Emin Köse ◽  
Beste Aydin ◽  
Caner Geyik ◽  
Öykü Gönül Geyik ◽  
Engin Ulukaya
Keyword(s):  
Tumor Microenvironment ◽  
Nucleic Acids ◽  
Cancer Cells ◽  
Tumor Formation ◽  
The Body ◽  
Biological Molecules ◽  
Pathological Conditions

: Exosomal vesicles enclose and carry a broad range of biological molecules, such as nucleic acids, lipids, and proteins, and transfer them between cells. In cancer, cells being mentioned could be neighbors in the same tumor microenvironment communicating with each other, or they could be localized at distant sites of the body, enabling suitable conditions for metastasis. Either way, it is a concrete fact that cells under physiological or pathological conditions make crosstalk via exosomal secretion. This review looks at the relation between exosomal cargo and mechanisms of cancer through recent research.

scholarly journals An Insight into the Roles of MicroRNAs and Exosomes in Sarcoma

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 428 ◽  
Author(s):  
Isaku Kohama ◽  
Nobuyoshi Kosaka ◽  
Hirotaka Chikuda ◽  
Takahiro Ochiya
Keyword(s):  
Gene Expression ◽  
Tumor Microenvironment ◽  
Solid Tumors ◽  
Extracellular Vesicles ◽  
Noncoding Rna ◽  
Premetastatic Niche ◽  
Related Disease ◽  
Distant Organ ◽  
Insight Into

Sarcomas are rare solid tumors, but at least one-third of patients with sarcoma die from tumor-related disease. MicroRNA (miRNA) is a noncoding RNA that regulates gene expression in all cells and plays a key role in the progression of cancers. Recently, it was identified that miRNAs are transferred between cells by enclosure in extracellular vesicles, especially exosomes. The exosome is a 100 nm-sized membraned vesicle that is secreted by many kinds of cells and contains miRNA, mRNA, DNA, and proteins. Cancer uses exosomes to influence not only the tumor microenvironment but also the distant organ to create a premetastatic niche. The progression of sarcoma is also regulated by miRNAs and exosomes. These miRNAs and exosomes can be targeted as biomarkers and treatments. In this review, we summarize the studies of miRNA and exosomes in sarcoma.

scholarly journals The Role of Cancer-Associated Fibroblasts and Extracellular Vesicles in Tumorigenesis

2020 ◽  
Vol 21 (18) ◽  
pp. 6837 ◽  
Author(s):  
Issraa Shoucair ◽  
Fernanda Weber Mello ◽  
James Jabalee ◽  
Saeideh Maleki ◽  
Cathie Garnis
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Therapy Resistance ◽  
The Other ◽  
Cancer Associated Fibroblasts ◽  
Metastatic Niche ◽  
Niche Formation ◽  
Molecular Aspects

Extracellular vesicles (EVs) play a key role in the communication between cancer cells and stromal components of the tumor microenvironment (TME). In this context, cancer cell-derived EVs can regulate the activation of a CAF phenotype in TME cells, which can be mediated by several EV cargos (e.g., miRNA, proteins, mRNA and lncRNAs). On the other hand, CAF-derived EVs can mediate several processes during tumorigenesis, including tumor growth, invasion, metastasis, and therapy resistance. This review aimed to discuss the molecular aspects of EV-based cross-talk between CAFs and cancer cells during tumorigenesis, in addition to assessing the roles of EV cargo in therapy resistance and pre-metastatic niche formation.

scholarly journals Extracellular Vesicles and Cancer: A Focus on Metabolism, Cytokines, and Immunity

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 171 ◽  
Author(s):  
Donatella Lucchetti ◽  
Claudio Ricciardi Tenore ◽  
Filomena Colella ◽  
Alessandro Sgambato
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cell Fate ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Cell Communication ◽  
Metabolic Effects ◽  
Metabolic Phenotype ◽  
Metabolic Switch

A better understanding of the mechanisms of cell communication between cancer cells and the tumor microenvironment is crucial to develop personalized therapies. It has been known for a while that cancer cells are metabolically distinct from other non-transformed cells. This metabolic phenotype is not peculiar to cancer cells but reflects the characteristics of the tumor microenvironment. Recently, it has been shown that extracellular vesicles are involved in the metabolic switch occurring in cancer and tumor-stroma cells. Moreover, in an immune system, the metabolic programs of different cell subsets are distinctly associated with their immunological function, and extracellular vesicles could be a key factor in the shift of cell fate modulating cancer immunity. Indeed, during tumor progression, tumor-associated immune cells and fibroblasts acquire a tumor-supportive and anti-inflammatory phenotype due to their interaction with tumor cells and several findings suggest a role of extracellular vesicles in this phenomenon. This review aims to collect all the available evidence so far obtained on the role of extracellular vesicles in the modulation of cell metabolism and immunity. Moreover, we discuss the possibility for extracellular vesicles of being involved in drug resistance mechanisms, cancer progression and metastasis by inducing immune-metabolic effects on surrounding cells.

Extracellular vesicles in cancer progression: are they part of the problem or part of the solution?

Nanomedicine ◽  
2020 ◽  
Vol 15 (26) ◽  
pp. 2625-2641
Author(s):  
Juliete Nathali Scholl ◽  
Camila Kehl Dias ◽  
Laurent Muller ◽  
Ana Maria Oliveira Battastini ◽  
Fabrício Figueiró
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Immune Cells ◽  
Cell Function ◽  
Cytokine Release

Extracellular vesicles (EVs) are released especially by cancer cells. They modulate the tumor microenvironment by interacting with immune cells while carrying immunosuppressive or immunostimulatory molecules. In this review, we will explore some conflicting reports regarding the immunological outcomes of EVs in cancer progression, in which they might initiate an antitumor immune response or an immunosuppressive response. Concerning immunosuppression, the role of tumor-derived EVs’ in the adenosinergic system is underexplored. The enhancement of adenosine (ADO) levels in the tumor microenvironment impairs T-cell function and cytokine release. However, some tumor-derived EVs may deliver immunostimulatory factors, promoting immunogenic activity, even with ADO production. The modulatory role of ADO over the tumor progression represents a piece in an intricate microenvironment with anti and pro tumoral seesaw-like mechanisms.

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