scholarly journals Extracellular Vesicles Are Key Regulators of Tumor Neovasculature

2020 ◽  
Vol 8 ◽  
Author(s):  
Naoya Kuriyama ◽  
Yusuke Yoshioka ◽  
Shinsuke Kikuchi ◽  
Nobuyoshi Azuma ◽  
Takahiro Ochiya
Keyword(s):  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Tumor Angiogenesis ◽  
Current Knowledge ◽  
Cell Communication ◽  
Multiple Roles ◽  
Mesenchymal Transition ◽  
Surrounding Environment ◽  
Endothelial To Mesenchymal Transition ◽  
Review Current

Tumor progression involves a series of biologically important steps in which the crosstalk between cancer cells and the surrounding environment is an important issue. Angiogenesis is a key tumorigenic phenomenon for cancer progression. Tumor-related extracellular vesicles (EVs) modulate the tumor microenvironment (TME) through cell-to-cell communication. Tumor cells in a hypoxic TME release more EVs than cells in a normoxic environment due to uncontrollable tumor proliferation. Tumor-derived EVs in the TME influence endothelial cells (ECs), which then play multiple roles, contributing to tumor angiogenesis, loss of the endothelial vascular barrier by binding to ECs, and subsequent endothelial-to-mesenchymal transition. In contrast, they also indirectly induce tumor angiogenesis through the phenotype switching of various cells into cancer-associated fibroblasts, the activation of tumor-associated ECs and platelets, and remodeling of the extracellular matrix. Here, we review current knowledge regarding the involvement of EVs in tumor vascular-related cancer progression.

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

2019 ◽  
Vol 20 (10) ◽  
pp. 2584 ◽  
Author(s):  
Shinsuke Kikuchi ◽  
Yusuke Yoshioka ◽  
Marta Prieto-Vila ◽  
Takahiro Ochiya
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Current Knowledge ◽  
Cell Communication ◽  
Matrix Remodeling ◽  
Mesenchymal Transition ◽  
Patients With Cancer ◽  
Tumor Environment ◽  
Endothelial To Mesenchymal Transition

The primary cause of mortality among patients with cancer is the progression of the tumor, better known as cancer invasion and metastasis. Cancer progression involves a series of biologically important steps in which the cross-talk between cancer cells and the cells in the surrounding environment is positioned as an important issue. Notably, angiogenesis is a key tumorigenic phenomenon for cancer progression. Cancer-related extracellular vesicles (EVs) commonly contribute to the modulation of a microenvironment favorable to cancer cells through their function of cell-to-cell communication. Vascular-related cells such as endothelial cells (ECs) and platelets activated by cancer cells and cancer-derived EVs develop procoagulant and proinflammatory statuses, which help excite the tumor environment, and play major roles in tumor progression, including in tumor extravasation, tumor cell microthrombi formation, platelet aggregation, and metastasis. In particular, cancer-derived EVs influence ECs, which then play multiple roles such as contributing to tumor angiogenesis, loss of endothelial vascular barrier by binding to ECs, and the subsequent endothelial-to-mesenchymal transition, i.e., extracellular matrix remodeling. Thus, cell-to-cell communication between cancer cells and ECs via EVs may be an important target for controlling cancer progression. This review describes the current knowledge regarding the involvement of EVs, especially exosomes derived from cancer cells, in EC-related cancer progression.

scholarly journals Multiple Roles of Exosomal Long Noncoding RNAs in Cancers

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Wenyuan Zhao ◽  
Yuanqi Liu ◽  
Chunfang Zhang ◽  
Chaojun Duan
Keyword(s):  
Extracellular Vesicles ◽  
Cancer Diagnosis ◽  
Tumor Angiogenesis ◽  
Cell Communication ◽  
Noncoding Rnas ◽  
Multiple Roles ◽  
Long Noncoding Rnas ◽  
Cancer Therapies ◽  
Transcriptional Noise ◽  
Intercellular Exchange

Long noncoding RNAs (lncRNAs) are not transcriptional noise, as previously understood, but are currently considered to be multifunctional. Exosomes are derived from the internal multivesicular compartment and are extracellular vesicles (EVs) with diameters of 30–100 nm. Exosomes play significant roles in the intercellular exchange of information and material. Exosomal lncRNAs may be promising biomarkers for cancer diagnosis and potential targets for cancer therapies, since they are increasingly understood to be involved in tumorigenesis, tumor angiogenesis, and chemoresistance. This review mainly focuses on the roles of emerging exosomal lncRNAs in cancer. In addition, the biogenesis of exosomes, the functions of lncRNAs, and the mechanisms of lncRNAs in exosome-mediated cell-cell communication are also summarized.

Extracellular vesicles: their role in cancer biology and epithelial–mesenchymal transition

2016 ◽  
Vol 474 (1) ◽  
pp. 21-45 ◽  
Author(s):  
Shashi K. Gopal ◽  
David W. Greening ◽  
Alin Rai ◽  
Maoshan Chen ◽  
Rong Xu ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Cancer Biology ◽  
Epithelial Mesenchymal Transition ◽  
Current Knowledge ◽  
Cell Communication ◽  
Metastatic Potential ◽  
Messenger Rnas ◽  
Mesenchymal Transition ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Cell–cell communication is critical across an assortment of physiological and pathological processes. Extracellular vesicles (EVs) represent an integral facet of intercellular communication largely through the transfer of functional cargo such as proteins, messenger RNAs (mRNAs), microRNA (miRNAs), DNAs and lipids. EVs, especially exosomes and shed microvesicles, represent an important delivery medium in the tumour micro-environment through the reciprocal dissemination of signals between cancer and resident stromal cells to facilitate tumorigenesis and metastasis. An important step of the metastatic cascade is the reprogramming of cancer cells from an epithelial to mesenchymal phenotype (epithelial–mesenchymal transition, EMT), which is associated with increased aggressiveness, invasiveness and metastatic potential. There is now increasing evidence demonstrating that EVs released by cells undergoing EMT are reprogrammed (protein and RNA content) during this process. This review summarises current knowledge of EV-mediated functional transfer of proteins and RNA species (mRNA, miRNA, long non-coding RNA) between cells in cancer biology and the EMT process. An in-depth understanding of EVs associated with EMT, with emphasis on molecular composition (proteins and RNA species), will provide fundamental insights into cancer biology.

scholarly journals Extracellular Vesicles Containing MicroRNA-92a-3p Facilitate Partial Endothelial-Mesenchymal Transition and Angiogenesis in Endothelial Cells

2019 ◽  
Vol 20 (18) ◽  
pp. 4406 ◽  
Author(s):  
Nami O. Yamada ◽  
Kazuki Heishima ◽  
Yukihiro Akao ◽  
Takao Senda
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Extracellular Vesicles ◽  
Epithelial To Mesenchymal Transition ◽  
Ectopic Expression ◽  
Cell Communication ◽  
Related Gene ◽  
Mesenchymal Transition ◽  
Essential Components ◽  
Endothelial To Mesenchymal Transition

Extracellular vesicles (EVs) are nanometer-sized membranous vesicles used for primitive cell-to-cell communication. We previously reported that colon cancer-derived EVs contain abundant miR-92a-3p and have a pro-angiogenic function. We previously identified Dickkopf-3 (Dkk-3) as a direct target of miR-92a-3p; however, the pro-angiogenic function of miR-92a-3p cannot only be attributed to downregulation of Dkk-3. Therefore, the complete molecular mechanism by which miR-92a-3p exerts pro-angiogenic effects is still unclear. Here, we comprehensively analyzed the gene sets affected by ectopic expression of miR-92a-3p in endothelial cells to elucidate processes underlying EV-induced angiogenesis. We found that the ectopic expression of miR-92a-3p upregulated cell cycle- and mitosis-related gene expression and downregulated adhesion-related gene expression in endothelial cells. We also identified a novel target gene of miR-92a-3p, claudin-11. Claudin-11 belongs to the claudin gene family, which encodes essential components expressed at tight junctions (TJs). Disruption of TJs with a concomitant loss of claudin expression is a significant event in the process of epithelial-to-mesenchymal transition. Our findings have unveiled a new EV-mediated mechanism for tumor angiogenesis through the induction of partial endothelial-to-mesenchymal transition in endothelial cells.

scholarly journals The Contribution of Endothelial-Mesenchymal Transition to Atherosclerosis

2021 ◽  
Vol 1 (1) ◽  
pp. 39-54
Author(s):  
Jinyu Zhang ◽  
Stella C. Ogbu ◽  
Phillip R. Musich ◽  
Douglas P. Thewke ◽  
Zhiqiang Yao ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Vascular Inflammation ◽  
Mesenchymal Phenotype ◽  
Mesenchymal Transition ◽  
Common Chronic Disease ◽  
Complex Process ◽  
Endothelial To Mesenchymal Transition ◽  
Key Pathways ◽  
Endothelial Mesenchymal Transition ◽  
Progression Of Atherosclerosis

Atherosclerosis is a chronic progressive condition in which the wall of the artery develops abnormalities and causes thickening of the blood vessels. The development of atherosclerosis is a complex process characterized by vascular inflammation and the growth of atherosclerotic plaques that eventually lead to compromised blood flow. The endothelial to mesenchymal transition (EndMT) is a phenomenon whereby endothelial cells lose their endothelial properties and acquire a mesenchymal phenotype similar to myofibroblast and smooth muscle cells. This process is considered a key contributor to the development and, importantly, the progression of atherosclerosis. Thus, therapeutically targeting the EndMT will provide a broad strategy to attenuate the development of atherosclerosis. Here, we review our current knowledge of EndMT in atherosclerosis including several key pathways such as hypoxia, TGF-β signaling, inflammation, and environmental factors during the development of atherosclerosis. In addition, we discuss several transgenic mouse models for studying atherosclerosis. Taken together, rapidly accelerating knowledge and continued studies promise further progress in preventing this common chronic disease.

scholarly journals Cell-to-Cell Communication by Host-Released Extracellular Vesicles in the Gut: Implications in Health and Disease

2021 ◽  
Vol 22 (4) ◽  
pp. 2213
Author(s):  
Natalia Diaz-Garrido ◽  
Cecilia Cordero ◽  
Yenifer Olivo-Martinez ◽  
Josefa Badia ◽  
Laura Baldomà
Keyword(s):  
Extracellular Vesicles ◽  
Intestinal Mucosa ◽  
Current Knowledge ◽  
Cell Communication ◽  
Bioactive Molecules ◽  
Target Cells ◽  
Immune Functions ◽  
Intestinal Homeostasis ◽  
General Terms ◽  
Health And Disease

Communication between cells is crucial to preserve body homeostasis and health. Tightly controlled intercellular dialog is particularly relevant in the gut, where cells of the intestinal mucosa are constantly exposed to millions of microbes that have great impact on intestinal homeostasis by controlling barrier and immune functions. Recent knowledge involves extracellular vesicles (EVs) as mediators of such communication by transferring messenger bioactive molecules including proteins, lipids, and miRNAs between cells and tissues. The specific functions of EVs principally depend on the internal cargo, which upon delivery to target cells trigger signal events that modulate cellular functions. The vesicular cargo is greatly influenced by genetic, pathological, and environmental factors. This finding provides the basis for investigating potential clinical applications of EVs as therapeutic targets or diagnostic biomarkers. Here, we review current knowledge on the biogenesis and cargo composition of EVs in general terms. We then focus the attention to EVs released by cells of the intestinal mucosa and their impact on intestinal homeostasis in health and disease. We specifically highlight their role on epithelial barrier integrity, wound healing of epithelial cells, immunity, and microbiota shaping. Microbiota-derived EVs are not reviewed here.

scholarly journals Snail Overexpression Alters the microRNA Content of Extracellular Vesicles Released from HT29 Colorectal Cancer Cells and Activates Pro-Inflammatory State In Vivo

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 172
Author(s):  
Izabela Papiewska-Pająk ◽  
Patrycja Przygodzka ◽  
Damian Krzyżanowski ◽  
Kamila Soboska ◽  
Izabela Szulc-Kiełbik ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Colorectal Cancer Cells ◽  
Microrna Profile ◽  
Inflammatory State ◽  
Metastatic Process

During metastasis, cancer cells undergo phenotype changes in the epithelial-mesenchymal transition (EMT) process. Extracellular vesicles (EVs) released by cancer cells are the mediators of intercellular communication and play a role in metastatic process. Knowledge of factors that influence the modifications of the pre-metastatic niche for the migrating carcinoma cells is important for prevention of metastasis. We focus here on how cancer progression is affected by EVs released from either epithelial-like HT29-cells or from cells that are in early EMT stage triggered by Snail transcription factor (HT29-Snail). We found that EVs released from HT29-Snail, as compared to HT29-pcDNA cells, have a different microRNA profile. We observed the presence of interstitial pneumonias in the lungs of mice injected with HT29-Snail cells and the percent of mice with lung inflammation was higher after injection of HT29-Snail-EVs. Incorporation of EVs released from HT29-pcDNA, but not released from HT29-Snail, leads to the increased secretion of IL-8 from macrophages. We conclude that Snail modifications of CRC cells towards more invasive phenotype also alter the microRNA cargo of released EVs. The content of cell-released EVs may serve as a biomarker that denotes the stage of CRC and EVs-specific microRNAs may be a target to prevent cancer progression.

scholarly journals Extracellular Vesicles: An Emerging Nanoplatform for Cancer Therapy

2021 ◽  
Vol 10 ◽  
Author(s):  
Yifan Ma ◽  
Shiyan Dong ◽  
Xuefeng Li ◽  
Betty Y. S. Kim ◽  
Zhaogang Yang ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Extracellular Vesicles ◽  
Drug Delivery Systems ◽  
Current Knowledge ◽  
Drug Loading ◽  
Cell Communication ◽  
Cancer Therapies ◽  
Therapeutic Function ◽  
Cancer Studies ◽  
Potential Use

Extracellular vesicles (EVs) are cell-derived membrane particles that represent an endogenous mechanism for cell-to-cell communication. Since discovering that EVs have multiple advantages over currently available delivery platforms, such as their ability to overcome natural barriers, intrinsic cell targeting properties, and circulation stability, the potential use of EVs as therapeutic nanoplatforms for cancer studies has attracted considerable interest. To fully elucidate EVs’ therapeutic function for treating cancer, all current knowledge about cellular uptake and trafficking of EVs will be initially reviewed. In order to further improve EVs as anticancer therapeutics, engineering strategies for cancer therapy have been widely explored in the last decade, along with other cancer therapies. However, therapeutic applications of EVs as drug delivery systems have been limited because of immunological concerns, lack of methods to scale EV production, and efficient drug loading. We will review and discuss recent progress and remaining challenges in developing EVs as a delivery nanoplatform for cancer therapy.

scholarly journals Microenvironmental Hypoxia Induces Dynamic Changes in Lung Cancer Synthesis and Secretion of Extracellular Vesicles

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2917
Author(s):  
Shun Wilford Tse ◽  
Chee Fan Tan ◽  
Jung Eun Park ◽  
JebaMercy Gnanasekaran ◽  
Nikhil Gupta ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Membrane Trafficking ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Functional Clustering ◽  
Signalling Molecules ◽  
Proteomic Approach

Extracellular vesicles (EVs) mediate critical intercellular communication within healthy tissues, but are also exploited by tumour cells to promote angiogenesis, metastasis, and host immunosuppression under hypoxic stress. We hypothesize that hypoxic tumours synthesize hypoxia-sensitive proteins for packing into EVs to modulate their microenvironment for cancer progression. In the current report, we employed a heavy isotope pulse/trace quantitative proteomic approach to study hypoxia sensitive proteins in tumour-derived EVs protein. The results revealed that hypoxia stimulated cells to synthesize EVs proteins involved in enhancing tumour cell proliferation (NRSN2, WISP2, SPRX1, LCK), metastasis (GOLM1, STC1, MGAT5B), stemness (STC1, TMEM59), angiogenesis (ANGPTL4), and suppressing host immunity (CD70). In addition, functional clustering analyses revealed that tumour hypoxia was strongly associated with rapid synthesis and EV loading of lysosome-related hydrolases and membrane-trafficking proteins to enhance EVs secretion. Moreover, lung cancer-derived EVs were also enriched in signalling molecules capable of inducing epithelial-mesenchymal transition in recipient cancer cells to promote their migration and invasion. Together, these data indicate that lung-cancer-derived EVs can act as paracrine/autocrine mediators of tumorigenesis and metastasis in hypoxic microenvironments. Tumour EVs may, therefore, offer novel opportunities for useful biomarkers discovery and therapeutic targeting of different cancer types and at different stages according to microenvironmental conditions.

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