Emerging role of extracellular vesicles in mediating cancer cachexia

2018 ◽  
Vol 46 (5) ◽  
pp. 1129-1136 ◽  
Author(s):  
Sai V. Chitti ◽  
Pamali Fonseka ◽  
Suresh Mathivanan
Keyword(s):  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Tissue Repair ◽  
Skeletal Muscles ◽  
Cancer Cachexia ◽  
Cell Communication ◽  
Rapid Weight Loss ◽  
Rapid Loss ◽  
Patients Experience

Cancer cachexia is a multifactorial metabolic syndrome characterized by the rapid loss of skeletal muscle mass with or without the loss of fat mass. Nearly 50–80% of all cancer patients' experience rapid weight loss results in ∼20% of cancer-related deaths. The levels of pro-inflammatory and pro-cachectic factors were significantly up-regulated in cachexia patients when compared with the patients who were without cachexia. It is becoming evident that these factors work synergistically to induce cancer cachexia. Extracellular vesicles (EVs) including exosomes and microvesicles are implicated in cell–cell communication, immune response, tissue repair, epigenetic regulation, and in various diseases including cancer. It has been reported that these EVs regulate cancer progression, metastasis, organotropism and chemoresistance. In recent times, the role of EVs in regulating cancer cachexia is beginning to unravel. The aim of this mini article is to review the recent knowledge gained in the field of EVs and cancer cachexia. Specifically, the role of tumour cell-derived EVs in promoting catabolism in distally located skeletal muscles and adipose tissue will be discussed.

scholarly journals The Power of Extracellular Vesicles in Myeloproliferative Neoplasms: “Crafting” a Microenvironment That Matters

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2316
Author(s):  
Lucia Catani ◽  
Michele Cavo ◽  
Francesca Palandri
Keyword(s):  
Extracellular Vesicles ◽  
Immune Escape ◽  
Myeloproliferative Neoplasms ◽  
Cell Communication ◽  
Bioactive Molecules ◽  
Driver Genes ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Patients Experience

Myeloproliferative Neoplasms (MPN) are acquired clonal disorders of the hematopoietic stem cells and include Essential Thrombocythemia, Polycythemia Vera and Myelofibrosis. MPN are characterized by mutations in three driver genes (JAK2, CALR and MPL) and by a state of chronic inflammation. Notably, MPN patients experience increased risk of thrombosis, disease progression, second neoplasia and evolution to acute leukemia. Extracellular vesicles (EVs) are a heterogeneous population of microparticles with a role in cell-cell communication. The EV-mediated cross-talk occurs via the trafficking of bioactive molecules such as nucleic acids, proteins, metabolites and lipids. Growing interest is focused on EVs and their potential impact on the regulation of blood cancers. Overall, EVs have been suggested to orchestrate the complex interplay between tumor cells and the microenvironment with a pivotal role in “education” and “crafting” of the microenvironment by regulating angiogenesis, coagulation, immune escape and drug resistance of tumors. This review is focused on the role of EVs in MPN. Specifically, we will provide an overview of recent findings on the involvement of EVs in MPN pathogenesis and discuss opportunities for their potential application as diagnostic and prognostic biomarkers.

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.

scholarly journals The Role of Exosomes in Cancer Progression

2021 ◽  
Vol 23 (1) ◽  
pp. 8
Author(s):  
Beáta Soltész ◽  
Gergely Buglyó ◽  
Nikolett Németh ◽  
Melinda Szilágyi ◽  
Ondrej Pös ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Cell Communication ◽  
Apoptotic Bodies ◽  
Practical Application ◽  
Tumor Microenvironments ◽  
Metastasis Development

Early detection, characterization and monitoring of cancer are possible by using extracellular vesicles (EVs) isolated from non-invasively obtained liquid biopsy samples. They play a role in intercellular communication contributing to cell growth, differentiation and survival, thereby affecting the formation of tumor microenvironments and causing metastases. EVs were discovered more than seventy years ago. They have been tested recently as tools of drug delivery to treat cancer. Here we give a brief review on extracellular vesicles, exosomes, microvesicles and apoptotic bodies. Exosomes play an important role by carrying extracellular nucleic acids (DNA, RNA) in cell-to-cell communication causing tumor and metastasis development. We discuss the role of extracellular vesicles in the pathogenesis of cancer and their practical application in the early diagnosis, follow up, and next-generation treatment of cancer patients.

scholarly journals B-Cell Activating Factor as a Cancer Biomarker and Its Implications in Cancer-Related Cachexia

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Michal Rihacek ◽  
Julie Bienertova-Vasku ◽  
Dalibor Valik ◽  
Jaroslav Sterba ◽  
Katerina Pilatova ◽  
...  
Keyword(s):  
B Cell ◽  
Cancer Progression ◽  
Lupus Erythematosus ◽  
Cancer Cachexia ◽  
Plasma Cells ◽  
Ongoing Research ◽  
B Cell Activating Factor ◽  
Proinflammatory Role ◽  
Cachexia Syndrome

B-cell activating factor (BAFF) is a cytokine and adipokine of the TNF ligand superfamily. The main biological function of BAFF in maintaining the maturation of B-cells to plasma cells has recently made it a target of the first FDA-approved selective BAFF antibody, belimumab, for the therapy of systemic lupus erythematosus. Concomitantly, the role of BAFF in cancer has been a subject of research since its discovery. Here we review BAFF as a biomarker of malignant disease activity and prognostic factor in B-cell derived malignancies such as multiple myeloma. Moreover, anti-BAFF therapy seems to be a promising approach in treatment of B-cell derived leukemias/lymphomas. In nonhematologic solid tumors, BAFF may contribute to cancer progression by mechanisms both dependent on and independent of BAFF’s proinflammatory role. We also describe ongoing research into the pathophysiological link between BAFF and cancer-related cachexia. BAFF has been shown to contribute to inflammation and insulin resistance which are known to worsen cancer cachexia syndrome. Taking all the above together, BAFF is emerging as a biomarker of several malignancies and a possible hallmark of cancer cachexia.

scholarly journals Platelet Extracellular Vesicles

2020 ◽  
Author(s):  
Florian Puhm ◽  
Eric Boilard ◽  
Kellie R. Machlus
Keyword(s):  
Bone Marrow ◽  
Synovial Fluid ◽  
Nucleic Acids ◽  
Extracellular Vesicles ◽  
Cell Communication ◽  
Biological Processes ◽  
Vascular Integrity ◽  
Pathological Conditions ◽  
Broad Array

Extracellular vesicles (EVs) are a means of cell-to-cell communication and can facilitate the exchange of a broad array of molecules between adjacent or distant cells. Platelets are anucleate cells derived from megakaryocytes and are primarily known for their role in maintaining hemostasis and vascular integrity. Upon activation by a variety of agonists, platelets readily generate EVs, which were initially identified as procoagulant particles. However, as both platelets and their EVs are abundant in blood, the role of platelet EVs in hemostasis may be redundant. Moreover, findings have challenged the significance of platelet-derived EVs in coagulation. Looking beyond hemostasis, platelet EV cargo is incredibly diverse and can include lipids, proteins, nucleic acids, and organelles involved in numerous other biological processes. Furthermore, while platelets cannot cross tissue barriers, their EVs can enter lymph, bone marrow, and synovial fluid. This allows for the transfer of platelet-derived content to cellular recipients and organs inaccessible to platelets. This review highlights the importance of platelet-derived EVs in physiological and pathological conditions beyond hemostasis.

scholarly journals Emerging role of extracellular vesicles in liver diseases

2019 ◽  
Vol 317 (5) ◽  
pp. G739-G749 ◽  
Author(s):  
Harmeet Malhi
Keyword(s):  
Extracellular Vesicles ◽  
Cell Communication ◽  
Cell Types ◽  
Cell Responses ◽  
Therapeutic Delivery ◽  
Disease States ◽  
Therapeutic Uses ◽  
Potential Biomarker ◽  
Secretion Pathways

Extracellular vesicles (EVs) are membrane-defined nanoparticles released by most cell types. The EVs released by cells may differ quantitatively and qualitatively from physiological states to disease states. There are several unique properties of EVs, including their proteins, lipids and nucleic acid cargoes, stability in circulation, and presence in biofluids, which make them a critical vector for cell-to-cell communication and impart utility as a biomarker. EVs may also serve as a vehicle for selective cargo secretion. Similarly, EV cargo may be selectively manipulated for targeted therapeutic delivery. In this review an overview is provided on the EV classification, biogenesis, and secretion pathways, which are conserved across cell types. Next, cargo characterization and effector cell responses are discussed in the context of nonalcoholic steatohepatitis, alcoholic hepatitis, and acetaminophen-induced liver injury. The review also discusses the potential biomarker and therapeutic uses of circulating EVs.

scholarly journals Extracellular Vesicles-Mediated Transfer of miRNA Let-7b from PC3 Cells to Macrophages

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1495
Author(s):  
Egidia Costanzi ◽  
Rita Romani ◽  
Paolo Scarpelli ◽  
Ilaria Bellezza
Keyword(s):  
Prostate Cancer ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Inflammatory Responses ◽  
Target Cells ◽  
Prostate Cell ◽  
Prostate Cancer Therapy ◽  
Reverse Transcription Quantitative Pcr ◽  
Pc3 Cells

Prostate-derived extracellular vesicles (pEVs) may represent a way to selectively transport cargo molecules from the producing cells to the target cells to allow biological events, both in physiological and pathological circumstances. pEVs cargo participates in the modulation of the inflammatory responses in physiological conditions and during cancer progression. In the present study, we examined the expression levels of miRNA Let-7b, in both precursor and mature forms, in noncancerous and cancerous prostate cell lines, PNT2 and PC3 respectively, and in their extracellular vesicles (EVs) using reverse-transcription quantitative PCR strategies. We showed that miRNA Let-7b was highly expressed in noncancerous cells and strongly decreased in cancerous PC3 cells, while the opposite was observed in the respective EVs, thus supporting the tumor suppressor role of miRNA Let7-b. We also demonstrated that miRNA Let-7b can be transferred to THP-1 cells via EVs, which are known to induce TAM-like polarization. Our results support the view that miRNA Let-7 b, contained in PC3-derived EVs, is associated with the increase in the miRNA Let7-b observed in TAM-like macrophages. Overall, our results indicate that circulating EV-loaded miRNA might be useful biomarkers for prostate cancer progression and might also support a possible use of pEVs as targets for prostate cancer therapy.

scholarly journals Role of Extracellular Vesicles (EVs) in Cell Stress Response and Resistance to Cancer Therapy

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 136 ◽  
Author(s):  
Clodagh O’Neill ◽  
Katie Gilligan ◽  
Róisín Dwyer
Keyword(s):  
Disease Progression ◽  
Extracellular Vesicles ◽  
Cell Communication ◽  
Underlying Disease ◽  
Cell Stress ◽  
Response To Therapy ◽  
Nanosized Particles ◽  
Resistance To Therapy ◽  
Cell Stress Response

Extracellular vesicles (EVs) are nanosized particles released by all cells that have been heralded as novel regulators of cell-to-cell communication. It is becoming increasingly clear that in response to a variety of stress conditions, cells employ EV-mediated intercellular communication to transmit a pro-survival message in the tumor microenvironment and beyond, supporting evasion of cell death and transmitting resistance to therapy. Understanding changes in EV cargo and secretion pattern during cell stress may uncover novel, targetable mechanisms underlying disease progression, metastasis and resistance to therapy. Further, the profile of EVs released into the circulation may provide a circulating biomarker predictive of response to therapy and indicative of microenvironmental conditions linked to disease progression, such as hypoxia. Continued progress in this exciting and rapidly expanding field of research will be dependent upon widespread adoption of transparent reporting standards and implementation of guidelines to establish a consensus on methods of EV isolation, characterisation and nomenclature employed.

scholarly journals Mitochondrial Transfer and Regulators of Mesenchymal Stromal Cell Function and Therapeutic Efficacy

2020 ◽  
Vol 8 ◽  
Author(s):  
Amina Mohammadalipour ◽  
Sandeep P. Dumbali ◽  
Pamela L. Wenzel
Keyword(s):  
Regenerative Medicine ◽  
Cancer Progression ◽  
Mesenchymal Stromal Cell ◽  
Tissue Repair ◽  
Stromal Cell ◽  
Nutrient Utilization ◽  
Metabolic Reprogramming ◽  
Mitochondrial Activity ◽  
Mitochondrial Transfer

Mesenchymal stromal cell (MSC) metabolism plays a crucial role in the surrounding microenvironment in both normal physiology and pathological conditions. While MSCs predominantly utilize glycolysis in their native hypoxic niche within the bone marrow, new evidence reveals the importance of upregulation in mitochondrial activity in MSC function and differentiation. Mitochondria and mitochondrial regulators such as sirtuins play key roles in MSC homeostasis and differentiation into mature lineages of the bone and hematopoietic niche, including osteoblasts and adipocytes. The metabolic state of MSCs represents a fine balance between the intrinsic needs of the cellular state and constraints imposed by extrinsic conditions. In the context of injury and inflammation, MSCs respond to reactive oxygen species (ROS) and damage-associated molecular patterns (DAMPs), such as damaged mitochondria and mitochondrial products, by donation of their mitochondria to injured cells. Through intercellular mitochondria trafficking, modulation of ROS, and modification of nutrient utilization, endogenous MSCs and MSC therapies are believed to exert protective effects by regulation of cellular metabolism in injured tissues. Similarly, these same mechanisms can be hijacked in malignancy whereby transfer of mitochondria and/or mitochondrial DNA (mtDNA) to cancer cells increases mitochondrial content and enhances oxidative phosphorylation (OXPHOS) to favor proliferation and invasion. The role of MSCs in tumor initiation, growth, and resistance to treatment is debated, but their ability to modify cancer cell metabolism and the metabolic environment suggests that MSCs are centrally poised to alter malignancy. In this review, we describe emerging evidence for adaptations in MSC bioenergetics that orchestrate developmental fate decisions and contribute to cancer progression. We discuss evidence and potential strategies for therapeutic targeting of MSC mitochondria in regenerative medicine and tissue repair. Lastly, we highlight recent progress in understanding the contribution of MSCs to metabolic reprogramming of malignancies and how these alterations can promote immunosuppression and chemoresistance. Better understanding the role of metabolic reprogramming by MSCs in tissue repair and cancer progression promises to broaden treatment options in regenerative medicine and clinical oncology.

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