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 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.

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 Hiding the road signs that lead to tumor immunity

2011 ◽  
Vol 208 (10) ◽  
pp. 1937-1940 ◽  
Author(s):  
David A. Schaer ◽  
Alexander M. Lesokhin ◽  
Jedd D. Wolchok
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Solid Tumors ◽  
Tumor Immunity ◽  
New Work ◽  
The Road ◽  
T Cell Infiltration ◽  
Road Signs

Tumors exploit many strategies to evade T cell–mediated destruction. For example, tumors can prevent T cell infiltration by modifying gene expression in the endothelial cells and pericytes that form their vasculature. New work showing that the T cell–attracting chemokine CCL2 can be posttranslationally modified in the tumor microenvironment adds another mechanism to the already formidable arsenal of immunoevasion tactics used by solid tumors.

scholarly journals Human retinal organoids release extracellular vesicles that regulate gene expression in target human retinal progenitor cells

2021 ◽  
Author(s):  
Jing Zhou ◽  
Miguel Flores-Bellver ◽  
Jianbo Pan ◽  
Alberto Benito-Martin ◽  
Cui Shi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Extracellular Vesicles ◽  
Noncoding Rna ◽  
Tissue Characterization ◽  
Retinal Development ◽  
Retinal Progenitor Cells ◽  
Retina Development ◽  
Retinal Tissue ◽  
Retinal Progenitor

AbstractThe mechanisms underlying retinal development have not been completely elucidated. Extracellular vesicles (EVs) are novel essential mediators of cell-to-cell communication with emerging roles in developmental processes. Nevertheless, the identification of EVs in human retinal tissue, characterization of their cargo, and analysis of their potential role in retina development has not been accomplished. Three-dimensional retinal tissue derived from human induced pluripotent stem cells (hiPSC) provide an ideal developmental system to achieve this goal. Here we report that hiPSC-derived retinal organoids release exosomes and microvesicles with small noncoding RNA cargo. EV miRNA cargo-predicted targetome correlates with GO pathways involved in mechanisms of retinogenesis relevant to specific developmental stages corresponding to hallmarks of native human retina development. Furthermore, uptake of EVs by human retinal progenitor cells leads to changes in gene expression correlated with EV miRNA cargo predicted gene targets, and mechanisms involved in retinal development, ganglion cell and photoreceptor differentiation and function.

scholarly journals Density of immunogenic antigens does not explain the presence or absence of the T-cell–inflamed tumor microenvironment in melanoma

2016 ◽  
Vol 113 (48) ◽  
pp. E7759-E7768 ◽  
Author(s):  
Stefani Spranger ◽  
Jason J. Luke ◽  
Riyue Bao ◽  
Yuanyuan Zha ◽  
Kyle M. Hernandez ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Solid Tumors ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Immune Infiltration ◽  
Cancer Testis

Melanoma metastases can be categorized by gene expression for the presence of a T-cell–inflamed tumor microenvironment, which correlates with clinical efficacy of immunotherapies. T cells frequently recognize mutational antigens corresponding to nonsynonymous somatic mutations (NSSMs), and in some cases shared differentiation or cancer–testis antigens. Therapies are being pursued to trigger immune infiltration into non–T-cell–inflamed tumors in the hope of rendering them immunotherapy responsive. However, whether those tumors express antigens capable of T-cell recognition has not been explored. To address this question, 266 melanomas from The Cancer Genome Atlas (TCGA) were categorized by the presence or absence of a T-cell–inflamed gene signature. These two subsets were interrogated for cancer–testis, differentiation, and somatic mutational antigens. No statistically significant differences were observed, including density of NSSMs. Focusing on hypothetical HLA-A2+binding scores, 707 peptides were synthesized, corresponding to all identified candidate neoepitopes. No differences were observed in measured HLA-A2 binding between inflamed and noninflamed cohorts. Twenty peptides were randomly selected from each cohort to evaluate priming and recognition by human CD8+T cells in vitro with 25% of peptides confirmed to be immunogenic in both. A similar gene expression profile applied to all solid tumors of TCGA revealed no association between T-cell signature and NSSMs. Our results indicate that lack of spontaneous immune infiltration in solid tumors is unlikely due to lack of antigens. Strategies that improve T-cell infiltration into tumors may therefore be able to facilitate clinical response to immunotherapy once antigens become recognized.

scholarly journals Human Retinal Organoids Release Extracellular Vesicles That Regulate Gene Expression in Target Human Retinal Progenitor Cells

2021 ◽  
Author(s):  
Jing Zhou ◽  
Miguel Flores-Bellver ◽  
Jianbo Pan ◽  
Alberto Benito-Martin ◽  
Cui Shi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Extracellular Vesicles ◽  
Noncoding Rna ◽  
Tissue Characterization ◽  
Retinal Development ◽  
Retinal Progenitor Cells ◽  
Retina Development ◽  
Retinal Tissue ◽  
Retinal Progenitor

Abstract The mechanisms underlying retinal development have not been completely elucidated. Extracellular vesicles (EVs) are novel essential mediators of cell-to-cell communication with emerging roles in developmental processes. Nevertheless, the identification of EVs in human retinal tissue, characterization of their cargo, and analysis of their potential role in retina development has not been accomplished. Three-dimensional retinal tissue derived from human induced pluripotent stem cells (hiPSC) provide an ideal developmental system to achieve this goal. Here we report that hiPSC-derived retinal organoids release exosomes and microvesicles with small noncoding RNA cargo. EV miRNA cargo-predicted targetome correlates with GO pathways involved in mechanisms of retinogenesis relevant to specific developmental stages corresponding to hallmarks of native human retina development. Furthermore, uptake of EVs by human retinal progenitor cells leads to changes in gene expression correlated with EV miRNA cargo predicted gene targets, and mechanisms involved in retinal development, ganglion cell and photoreceptor differentiation and function.

scholarly journals Visualizing Extracellular Vesicles and Their Function in 3D Tumor Microenvironment Models

2021 ◽  
Vol 22 (9) ◽  
pp. 4784
Author(s):  
Evran E. Ural ◽  
Victoria Toomajian ◽  
Ehsanul Hoque Apu ◽  
Mladen Veletic ◽  
Ilangko Balasingham ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Extracellular Vesicles ◽  
Cell Cultures ◽  
High Throughput Screening ◽  
Tumor Development ◽  
3D Culture ◽  
Complex Signals ◽  
Molecular Control ◽  
Premetastatic Niche ◽  
3D Cultures

Extracellular vesicles (EVs) are cell-derived nanostructures that mediate intercellular communication by delivering complex signals in normal tissues and cancer. The cellular coordination required for tumor development and maintenance is mediated, in part, through EV transport of molecular cargo to resident and distant cells. Most studies on EV-mediated signaling have been performed in two-dimensional (2D) monolayer cell cultures, largely because of their simplicity and high-throughput screening capacity. Three-dimensional (3D) cell cultures can be used to study cell-to-cell and cell-to-matrix interactions, enabling the study of EV-mediated cellular communication. 3D cultures may best model the role of EVs in formation of the tumor microenvironment (TME) and cancer cell-stromal interactions that sustain tumor growth. In this review, we discuss EV biology in 3D culture correlates of the TME. This includes EV communication between cell types of the TME, differences in EV biogenesis and signaling associated with differing scaffold choices and in scaffold-free 3D cultures and cultivation of the premetastatic niche. An understanding of EV biogenesis and signaling within a 3D TME will improve culture correlates of oncogenesis, enable molecular control of the TME and aid development of drug delivery tools based on EV-mediated signaling.

Nanoparticle-plasma Membrane Interactions: Thermodynamics, Toxicity and Cellular Response

2020 ◽  
Vol 27 (20) ◽  
pp. 3330-3345
Author(s):  
Ana G. Rodríguez-Hernández ◽  
Rafael Vazquez-Duhalt ◽  
Alejandro Huerta-Saquero
Keyword(s):  
Gene Expression ◽  
Immune Responses ◽  
Cellular Response ◽  
Cellular Level ◽  
Membrane Interactions ◽  
Daily Lives ◽  
Cellular Physiology ◽  
Associated Proteins ◽  
First Contact ◽  
Insight Into

Nanomaterials have become part of our daily lives, particularly nanoparticles contained in food, water, cosmetics, additives and textiles. Nanoparticles interact with organisms at the cellular level. The cell membrane is the first protective barrier against the potential toxic effect of nanoparticles. This first contact, including the interaction between the cell membranes -and associated proteins- and the nanoparticles is critically reviewed here. Nanoparticles, depending on their toxicity, can cause cellular physiology alterations, such as a disruption in cell signaling or changes in gene expression and they can trigger immune responses and even apoptosis. Additionally, the fundamental thermodynamics behind the nanoparticle-membrane and nanoparticle-proteins-membrane interactions are discussed. The analysis is intended to increase our insight into the mechanisms involved in these interactions. Finally, consequences are reviewed and discussed.

The Therapeutic Potential and Role of miRNA, lncRNA, and circRNA in Osteoarthritis

2019 ◽  
Vol 19 (4) ◽  
pp. 255-263 ◽  
Author(s):  
Yuangang Wu ◽  
Xiaoxi Lu ◽  
Bin Shen ◽  
Yi Zeng
Keyword(s):  
Gene Expression ◽  
Gene Therapy ◽  
Extracellular Matrix ◽  
Inflammatory Reaction ◽  
Noncoding Rna ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Protein Translation ◽  
Cochrane Library

Background: Osteoarthritis (OA) is a disease characterized by progressive degeneration, joint hyperplasia, narrowing of joint spaces, and extracellular matrix metabolism. Recent studies have shown that the pathogenesis of OA may be related to non-coding RNA, and its pathological mechanism may be an effective way to reduce OA. Objective: The purpose of this review was to investigate the recent progress of miRNA, long noncoding RNA (lncRNA) and circular RNA (circRNA) in gene therapy of OA, discussing the effects of this RNA on gene expression, inflammatory reaction, apoptosis and extracellular matrix in OA. Methods: The following electronic databases were searched, including PubMed, EMBASE, Web of Science, and the Cochrane Library, for published studies involving the miRNA, lncRNA, and circRNA in OA. The outcomes included the gene expression, inflammatory reaction, apoptosis, and extracellular matrix. Results and Discussion: With the development of technology, miRNA, lncRNA, and circRNA have been found in many diseases. More importantly, recent studies have found that RNA interacts with RNA-binding proteins to regulate gene transcription and protein translation, and is involved in various pathological processes of OA, thus becoming a potential therapy for OA. Conclusion: In this paper, we briefly introduced the role of miRNA, lncRNA, and circRNA in the occurrence and development of OA and as a new target for gene therapy.

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