scholarly journals Role for extracellular vesicles in the tumour microenvironment

2017 ◽  
Vol 373 (1737) ◽  
pp. 20160488 ◽  
Author(s):  
Ana O'Loghlen

Extracellular vesicles (EVs) are small-membrane vesicles secreted by most cells types with the role to provide intercellular communication both locally and systemically. The transfer of their content between cells, which includes nucleic acids, proteins and lipids, confers the means for these interactions and induces significant cellular behaviour changes in the receiving cell. EVs are implicated in the regulation of numerous physiological and pathological processes, including development and neurological and cardiovascular diseases. Importantly, it has been shown that EV signalling is essential in almost all the steps necessary for the progress of carcinomas, from primary tumours to metastasis. In this review, we will focus on the latest findings for EV biology in relation to cancer progression and the tumour microenvironment. This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.

2021 ◽  
Vol 90 (2) ◽  
pp. e516
Author(s):  
Przemysław Szałata ◽  
Anna-Maria Guner ◽  
Michalina Raczkowska ◽  
Julia Smyrek ◽  
Dominika Szaj ◽  
...  

microRNAs (miRNAs) are non-coding RNAs that regulate gene expression and protect cells from foreign nucleic acids. miRNA is produced in the nucleus and processed in the cytoplasm. These small nucleic acid molecules are released from cells to the extracellular matrix (extracellular miRNA, ex-miRNA) and reach blood plasma (circulating miRNA). Circulating miRNA can also be detected in other biological fluids, such as saliva, cerebrospinal fluid or urine, and it is usually carried by proteins or extracellular vesicles. Argonaute-miRNA, or miRNA-lipoprotein complex, protect miRNA from being degraded. The entrance of extracellular miRNA into a target cell is mediated by endocytosis and membrane fusion of extracellular vesicles. Additionally, miRNA can also be delivered in high-density lipoproteins by means of interactions with scavenger receptors. miRNAs absorbed into a cell can act as tumour promoters (oncomirs), or suppressors by inhibiting the translation process of the target mRNAs, thus, affecting cells in the tumour microenvironment. miRNA can impact other cells by supporting tumour growth, promoting angiogenesis and modulating the immune system. Molecular high-throughput methods are employed to detect circulating miRNA, and a potentially helpful diagnostic test has been designed to characterise the cancer type. In this review, we aim to summarise the itinerary of miRNAs from a source cell to a target cell, as well as to show how this class of small nucleic acids participates in intercellular communication. Finally, we highlight examples of miRNAs usage as potential molecular markers and discuss treatment approaches in clinical trials.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Shenglong Li

AbstractBone sarcomas are rare cancers accompanied by metastatic disease, mainly including osteosarcoma, Ewing sarcoma and chondrosarcoma. Extracellular vesicles (EVs) are membrane vesicles released by cells in the extracellular matrix, which carry important signal molecules, can stably and widely present in various body fluids, such as plasma, saliva and scalp fluid, spinal cord, breast milk, and urine liquid. EVs can transport almost all types of biologically active molecules (DNA, mRNA, microRNA (miRNA), proteins, metabolites, and even pharmacological compounds). In this review, we summarized the basic biological characteristics of EVs and focused on their application in bone sarcomas. EVs can be use as biomarker vehicles for diagnosis and prognosis in bone sarcomas. The role of EVs in bone sarcoma has been analyzed point-by-point. In the microenvironment of bone sarcoma, bone sarcoma cells, mesenchymal stem cells, immune cells, fibroblasts, osteoclasts, osteoblasts, and endothelial cells coexist and interact with each other. EVs play an important role in the communication between cells. Based on multiple functions in bone sarcoma, this review provides new ideas for the discovery of new therapeutic targets and new diagnostic analysis.


2017 ◽  
Vol 373 (1737) ◽  
pp. 20160479 ◽  
Author(s):  
Mercedes Tkach ◽  
Joanna Kowal ◽  
Clotilde Théry

In the past decade, cell-to-cell communication mediated by exosomes has attracted growing attention from biomedical scientists and physicians, leading to several recent publications in top-tier journals. Exosomes are generally defined as secreted membrane vesicles, or extracellular vesicles (EVs), corresponding to the intraluminal vesicles of late endosomal compartments, which are secreted upon fusion of multi-vesicular endosomes with the cell's plasma membrane. Cells, however, were shown to release other types of EVs, for instance, by direct budding off their plasma membrane. Some of these EVs share with exosomes major biophysical and biochemical characteristics, such as size, density and membrane orientation, which impose difficulties in their efficient separation. Despite frequent claims in the literature, whether exosomes really display more important patho/physiological functions, or are endowed with higher potential as diagnostic or therapeutic tools than other EVs, is not yet convincingly demonstrated. In this opinion article, we describe reasons for this lack of precision knowledge in the current stage of the EV field, we review recently described approaches to overcome these caveats, and we propose ways to improve our knowledge on the respective functions of distinct EVs, which will be crucial for future development of well-designed EV-based clinical applications. This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.


2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Chao-Hui Chang ◽  
Siim Pauklin

AbstractPancreatic cancer (PC) is one of the leading causes of cancer-related death worldwide due to delayed diagnosis and limited treatments. More than 90% of all pancreatic cancers are pancreatic ductal adenocarcinoma (PDAC). Extensive communication between tumour cells and other cell types in the tumour microenvironment have been identified which regulate cancer hallmarks during pancreatic tumorigenesis via secretory factors and extracellular vesicles (EVs). The EV-capsuled factors not only facilitate tumour growth locally, but also enter circulation and reach distant organs to construct a pre-metastatic niche. In this review, we delineate the key factors in pancreatic ductal adenocarcinoma derived EVs that mediate different tumour processes. Also, we highlight the factors that are related to the crosstalk with cancer stem cells/cancer-initiating cells (CSC/CIC), the subpopulation of cancer cells that can efficiently metastasize and resist currently used chemotherapies. Lastly, we discuss the potential of EV-capsuled factors in early diagnosis and antitumour therapeutic strategies.


Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2221
Author(s):  
Luis Enrique Cortés-Hernández ◽  
Zahra Eslami-S ◽  
Bruno Costa-Silva ◽  
Catherine Alix-Panabières

In cancer, many analytes can be investigated through liquid biopsy. They play fundamental roles in the biological mechanisms underpinning the metastatic cascade and provide clinical information that can be monitored in real time during the natural course of cancer. Some of these analytes (circulating tumor cells and extracellular vesicles) share a key feature: the presence of a phospholipid membrane that includes proteins, lipids and possibly nucleic acids. Most cell-to-cell and cell-to-matrix interactions are modulated by the cell membrane composition. To understand cancer progression, it is essential to describe how proteins, lipids and nucleic acids in the membrane influence these interactions in cancer cells. Therefore, assessing such interactions and the phospholipid membrane composition in different liquid biopsy analytes might be important for future diagnostic and therapeutic strategies. In this review, we briefly describe some of the most important surface components of circulating tumor cells and extracellular vesicles as well as their interactions, putting an emphasis on how they are involved in the different steps of the metastatic cascade and how they can be exploited by the different liquid biopsy technologies.


2020 ◽  
Vol 21 (18) ◽  
pp. 6486 ◽  
Author(s):  
Stefano Martellucci ◽  
Nicola Salvatore Orefice ◽  
Adriano Angelucci ◽  
Amalia Luce ◽  
Michele Caraglia ◽  
...  

Extracellular Vesicles (EVs) represent a heterogeneous population of membranous cell-derived structures, including cargo-oriented exosomes and microvesicles. EVs are functionally associated with intercellular communication and play an essential role in multiple physiopathological conditions. Shedding of EVs is frequently increased in malignancies and their content, including proteins and nucleic acids, altered during carcinogenesis and cancer progression. EVs-mediated intercellular communication between tumor cells and between tumor and stromal cells can modulate, through cargo miRNA, the survival, progression, and drug resistance in cancer conditions. These consolidated suggestions and EVs’ stability in bodily fluids have led to extensive investigations on the potential employment of circulating EVs-derived miRNAs as tumor biomarkers and potential therapeutic vehicles. In this review, we highlight the current knowledge about circulating EVs-miRNAs in human cancer and the application limits of these tools, discussing their clinical utility and challenges in functions such as in biomarkers and instruments for diagnosis, prognosis, and therapy.


2018 ◽  
Vol 62 (2) ◽  
pp. 177-191 ◽  
Author(s):  
Roberta Palmulli ◽  
Guillaume van Niel

The release of extracellular vesicles such as exosomes provides an attractive intercellular communication pathway. Exosomes are 30- to 150-nm membrane vesicles that are generated in endosomal compartment and act as intercellular mediators in both physiological and pathological context. Despite the growing interest in exosome functions, the mechanisms responsible for their biogenesis and secretion are still not completely understood. Knowledge about these mechanisms is important because they control the composition, and hence the function and secretion, of exosomes. Exosomes are produced as intraluminal vesicles in extremely dynamic endosomal organelles, which undergo various maturation processes in order to form multivesicular endosomes. Notably, the function of multivesicular endosomes is balanced between exosome secretion and lysosomal degradation. In the present review, we present and discuss each intracellular trafficking pathway that has been reported or proposed as regulating exosome biogenesis, with a particular focus on the importance of endosomal dynamics in sorting out cargo proteins to exosomes and to the secretion of multivesicular endosomes. An overall picture reveals several key mechanisms, which mainly act at the crossroads of endosomal pathways as regulatory checkpoints of exosome biogenesis.


Lab on a Chip ◽  
2021 ◽  
Author(s):  
Yi-Sin Chen ◽  
Charles Lai ◽  
Chihchen Chen ◽  
Gwo-Bin Lee

Cell-released, membrane-encapsulated extracellular vesicles (EVs) serve as a means of intercellular communication by delivering bioactive cargos including proteins, nucleic acids and lipids. EVs have been widely used for a variety...


2021 ◽  
Vol 11 ◽  
Author(s):  
Bo Zhang ◽  
Ming Zhao ◽  
Qianjin Lu

In the last two decades, extracellular vesicles (EVs) have aroused wide interest among researchers in basic and clinical research. EVs, small membrane vesicles are released by almost all kinds of cells into the extracellular environment. According to many recent studies, EVs participate in immunomodulation and play an important role in the pathogenesis of autoimmune diseases. In addition, EVs have great potential in the diagnosis and therapy of autoimmune diseases. Here, we reviewed the latest research advances on the functions and mechanisms of EVs and their roles in the pathogenesis, diagnosis, and treatment of rheumatoid arthritis and systemic lupus erythematosus.


2020 ◽  
Vol 7 (12) ◽  
pp. 312-322
Author(s):  
Swagata Bose ◽  
Shifu Aggarwal ◽  
Durg Vijai Singh ◽  
Narottam Acharya

Extracellular vesicles (EV), also known as membrane vesicles, are produced as an end product of secretion by both pathogenic and non-pathogenic bacteria. Several reports suggest that archaea, gram-negative bacteria, and eukaryotic cells secrete membrane vesicles as a means for cell-free intercellular communication. EVs influence intercellular communication by transferring a myriad of biomolecules including genetic information. Also, EVs have been implicated in many phenomena such as stress response, intercellular competition, lateral gene transfer, and pathogenicity. However, the cellular process of secreting EVs in gram-positive bacteria is less studied. A notion with the thick cell-walled microbes such as gram-positive bacteria is that the EV release is impossible among them. The role of gram-positive EVs in health and diseases is being studied gradually. Being nano-sized, the EVs from gram-positive bacteria carry a diversity of cargo compounds that have a role in bacterial competition, survival, invasion, host immune evasion, and infection. In this review, we summarise the current understanding of the EVs produced by gram-positive bacteria. Also, we discuss the functional aspects of these components while comparing them with gram-negative bacteria.


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