scholarly journals Extracellular Vesicles Involvement in the Modulation of the Glioblastoma Environment

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Fausta Ciccocioppo ◽  
Paola Lanuti ◽  
Marco Marchisio ◽  
Sebastiano Miscia
Keyword(s):  
Phenotypic Plasticity ◽  
Extracellular Vesicles ◽  
Tumour Microenvironment ◽  
Complex Model ◽  
Diagnostic Classification ◽  
Prognostic Information ◽  
Critical Feature ◽  
Primary Brain Tumour ◽  
Intercellular Signalling

Glioblastoma (GBM) is the most deadly primary brain tumour and is a paradigmatic example of heterogeneous cancer. Although expanding data propose the phenotypic plasticity exhibited by glioblastoma cells, as a critical feature involved in the tumour development and posttherapy recurrence, the central machinery responsible for their aggressiveness remains elusive. Despite decades of research, the complex biology of the glioblastoma is still unknown. Progress in genetic and epigenetic discoveries has improved diagnostic classification, prognostic information, and therapeutic planning. In the complex model of intercellular signalling, several studies have shown that extracellular vesicles have a key role in the intercellular communication among GBM cells and the tumour microenvironment modulation. The purpose of this review is to summarize the role of the EV-mediated intercellular crosstalk in the glioblastoma physiopathology.

scholarly journals Normoxic Tumour Extracellular Vesicles Modulate the Response of Hypoxic Cancer and Stromal Cells to Doxorubicin In Vitro

2020 ◽  
Vol 21 (17) ◽  
pp. 5951
Author(s):  
Laura Patras ◽  
Marcel H. A. M. Fens ◽  
Pieter Vader ◽  
Arjan Barendrecht ◽  
Alina Sesarman ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Extracellular Vesicles ◽  
Hypoxia Inducible Factor ◽  
B Cell Lymphoma ◽  
Tumour Microenvironment ◽  
Hypoxia Inducible Factor 1 ◽  
Apoptotic Protein ◽  
Donor Cells

Extracellular vesicles (EV) secreted in the tumour microenvironment (TME) are emerging as major antagonists of anticancer therapies by orchestrating the therapeutic outcome through altering the behaviour of recipient cells. Recent evidence suggested that chemotherapeutic drugs could be responsible for the EV-mediated tumour–stroma crosstalk associated with cancer cell drug resistance. Here, we investigated the capacity of tumour EV (TEV) secreted by normoxic and hypoxic (1% oxygen) C26 cancer cells after doxorubicin (DOX) treatment to alter the response of naïve C26 cells and RAW 264.7 macrophages to DOX. We observed that C26 cells were less responsive to DOX treatment under normoxia compared to hypoxia, and a minimally cytotoxic DOX concentration that mounted distinct effects on cell viability was selected for TEV harvesting. Homotypic and heterotypic pretreatment of naïve hypoxic cancer and macrophage-like cells with normoxic DOX-elicited TEV rendered these cells slightly less responsive to DOX treatment. The observed effects were associated with strong hypoxia-inducible factor 1-alpha (HIF-1α) induction and B-cell lymphoma–extra-large anti-apoptotic protein (Bcl-xL)-mediated anti-apoptotic response in normoxic DOX-treated TEV donor cells, being also tightly connected to the DOX-TEV-mediated HIF-1α induction, as well as Bcl-xL levels increasing in recipient cells. Altogether, our results could open new perspectives for investigating the role of chemotherapy-elicited TEV in the colorectal cancer TME and their modulatory actions on promoting drug resistance.

scholarly journals Functional role of extracellular vesicles and lipoproteins in the tumour microenvironment

2017 ◽  
Vol 373 (1737) ◽  
pp. 20160480 ◽  
Author(s):  
Julien A. Menard ◽  
Myriam Cerezo-Magaña ◽  
Mattias Belting
Keyword(s):  
Cancer Cell ◽  
Extracellular Vesicles ◽  
Heparan Sulphate ◽  
Cell Communication ◽  
Tumour Microenvironment ◽  
Stress Factors ◽  
Nutrient Sources ◽  
Exogenous Stress ◽  
Distinct Features

Cancer can be regarded as an invasive organ that exhibits unique plasticity provided by coordinated, cancer cell-stromal cell communication in the tumour microenvironment. Typical stress factors in the tumour niche, such as hypoxia and acidosis, are major drivers and modulators of these events. Recent findings reveal an important role of extracellular vesicles and lipoproteins in cancer cell adaption to exogenous stress. Adaptive mechanisms include stimulation of angiogenesis and increased metastasis. Here, we will discuss the similarities and distinct features of these endogenous nanoparticles and their roles as signalosomes and nutrient sources in cancer. We will focus on the accumulating evidence for a central role of cell-surface heparan sulphate proteoglycans in the uptake of extracellular vesicles and lipoproteins. This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.

scholarly journals Cisplatin induces the release of extracellular vesicles from ovarian cancer cells that can induce invasiveness and drug resistance in bystander cells

2017 ◽  
Vol 373 (1737) ◽  
pp. 20170065 ◽  
Author(s):  
Priya Samuel ◽  
Laura Ann Mulcahy ◽  
Fiona Furlong ◽  
Helen O. McCarthy ◽  
Susan Ann Brooks ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Extracellular Vesicles ◽  
Bystander Effect ◽  
Tumour Microenvironment ◽  
Ovarian Cancer Cells ◽  
Poor Overall Survival ◽  
Bystander Cells ◽  
Stressed Cells

Ovarian cancer has a poor overall survival that is partly caused by resistance to drugs such as cisplatin. Resistance can be acquired as a result of changes to the tumour or due to altered interactions within the tumour microenvironment. Extracellular vesicles (EVs), small lipid-bound vesicles that are loaded with macromolecular cargo and released by cells, are emerging as mediators of communication in the tumour microenvironment. We previously showed that EVs mediate the bystander effect, a phenomenon in which stressed cells can communicate with neighbouring naive cells leading to various effects including DNA damage; however, the role of EVs released following cisplatin treatment has not been tested. Here we show that treatment of cells with cisplatin led to the release of EVs that could induce invasion and increased resistance when taken up by bystander cells. This coincided with changes in p38 and JNK signalling, suggesting that these pathways may be involved in mediating the effects. We also show that EV uptake inhibitors could prevent this EV-mediated adaptive response and thus sensitize cells in vitro to the effects of cisplatin. Our results suggest that preventing pro-tumourigenic EV cross-talk during chemotherapy is a potential therapeutic target for improving outcome in ovarian cancer patients. This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.

scholarly journals MicroRNAs and miRceptors: a new mechanism of action for intercellular communication

2017 ◽  
Vol 373 (1737) ◽  
pp. 20160486 ◽  
Author(s):  
Muller Fabbri
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Mechanism Of Action ◽  
Intercellular Communication ◽  
Target Genes ◽  
Tumour Microenvironment ◽  
Signalling Pathways ◽  
Non Coding Rnas ◽  
Cancerous Cells

MicroRNAs (miRs) are small non-coding RNAs (ncRNAs) that control the expression of target genes by modulating (usually inhibiting) their translation into proteins. This ‘traditional’ mechanism of action of miRs has been recently challenged by new discoveries pointing towards a role of miRs as ‘hormones’, capable of binding to proteic receptors (miRceptors) and triggering their downstream signalling pathways. These findings harbour particular significance within the tumour microenvironment (TME), defined as the variety of non-cancerous cells surrounding cancer cells, but are relevant also for other diseases. In recent years it has become clearer that the TME does not passively assist the growth of cancer cells but contributes to its biology. Some of the mediators of the intercellular communication between cancer cells and TME are miRs shuttled within exosomes, a subtype of cellular released extracellular vesicles. This article will highlight the most recent findings on the biological implications of miR–miRceptor interactions for the biology of the TME and other diseases, and will provide some perspectives on the future development of this fascinating research. This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.

scholarly journals Tumour–adipose tissue crosstalk: fuelling tumour metastasis by extracellular vesicles

2017 ◽  
Vol 373 (1737) ◽  
pp. 20160485 ◽  
Author(s):  
Lucía Robado de Lope ◽  
Olwen Leaman Alcíbar ◽  
Ana Amor López ◽  
Marta Hergueta-Redondo ◽  
Héctor Peinado
Keyword(s):  
Adipose Tissue ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Cell Types ◽  
Tumour Microenvironment ◽  
Tumour Cells ◽  
Breast And Ovarian Cancer ◽  
Tumour Metastasis ◽  
Bone Marrow Derived Cells

During metastasis, tumour cells must communicate with their microenvironment by secreted soluble factors and extracellular vesicles. Different stromal cell types (e.g. bone marrow–derived cells, endothelial cells and fibroblasts) influence the growth and progression of tumours. In recent years, interest has extended to other cell types in the tumour microenvironment such as adipocytes and adipose tissue–derived mesenchymal stem cells. Indeed, obesity is becoming pandemic in some developing countries and it is now considered to be a risk factor for cancer progression. However, the true impact of obesity on the metastatic behaviour of tumours is still not yet fully understood. In this ‘Perspective’ article, we will discuss the potential influence of obesity on tumour metastasis, mainly in melanoma, breast and ovarian cancer. We summarize the main mechanisms involved with special attention to the role of extracellular vesicles in this process. We envisage that besides having a direct impact on tumour cells, obesity systemically preconditions the tumour microenvironment for future metastasis by favouring the formation of pro-inflammatory niches. This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.

scholarly journals Extracellular Vesicles as Mediators of Therapy Resistance in the Breast Cancer Microenvironment

Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 132
Author(s):  
Mark Samuels ◽  
Chiara Cilibrasi ◽  
Panagiotis Papanastasopoulos ◽  
Georgios Giamas
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Breast Cancer Cells ◽  
Therapy Resistance ◽  
Tumour Microenvironment ◽  
Cancer Microenvironment ◽  
Bidirectional Communication

Resistance to various therapies, including novel immunotherapies, poses a major challenge in the management of breast cancer and is the leading cause of treatment failure. Bidirectional communication between breast cancer cells and the tumour microenvironment is now known to be an important contributor to therapy resistance. Several studies have demonstrated that crosstalk with the tumour microenvironment through extracellular vesicles is an important mechanism employed by cancer cells that leads to drug resistance via changes in protein, lipid and nucleic acid cargoes. Moreover, the cargo content enables extracellular vesicles to be used as effective biomarkers for predicting response to treatments and as potential therapeutic targets. This review summarises the literature to date regarding the role of extracellular vesicles in promoting therapy resistance in breast cancer through communication with the tumour microenvironment.

Effect of Annexins Translocated in Extracellular Vesicles on Tumorigenesis

2020 ◽  
Vol 20 ◽  
Author(s):  
Qionghui Wu ◽  
Haidong Wei ◽  
Wenbo Meng ◽  
Xiaodong Xie ◽  
Zhenchang Zhang ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Extracellular Vesicles ◽  
Immune Cell ◽  
Epithelial Mesenchymal Transition ◽  
Main Role ◽  
Tumor Cell Adhesion ◽  
Mesenchymal Transition ◽  
Calcium Dependent ◽  
Tumor Neovascularization

: Annexin, a calcium-dependent phospholipid binding protein, can affect tumor cell adhesion, proliferation, apoptosis, invasion and metastasis, as well as tumor neovascularization in different ways. Recent studies have shown that annexin exists not only as an intracellular protein in tumor cells, but also in different ways to be secret outside the cell as a “crosstalk” tool for tumor cells and tumor microenvironment, thus playing an important role in the development of tumors, such as participating in epithelial-mesenchymal transition, regulating immune cell behavior, promoting neovascularization and so on. The mechanism of annexin secretion in the form of extracellular vesicles and its specific role is still unclear. This paper summarizes the main role of annexin secreted into the extracellular space in the form of extracellular vesicles in tumorigenesis and drug resistance and analyzes its possible mechanism.

The role of hormones

2018 ◽  
Author(s):  
H. Frederik Nijhout ◽  
Emily Laub
Keyword(s):  
Phenotypic Plasticity ◽  
Social Behavior ◽  
Parental Care ◽  
Juvenile Hormone ◽  
Reproductive Behavior ◽  
Hormonal Control ◽  
Plastic Trait

Many behaviors of insects are stimulated, modified, or modulated by hormones. The principal hormones involved are the same as the ones that control moulting, metamorphosis, and other aspects of development, principally ecdysone and juvenile hormone. In addition, a small handful of neurosecretory hormones are involved in the control of specific behaviors. Because behavior is a plastic trait, this chapter begins by outlining the biology and hormonal control of phenotypic plasticity in insects, and how the hormonal control of behavior fits in with other aspects of the control of phenotypic plasticity. The rest of the chapter is organized around the diversity of behaviors that are known to be controlled by or affected by hormones. These include eclosion and moulting behavior, the synthesis and release of pheromones, migration, parental care, dominance, reproductive behavior, and social behavior.

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