scholarly journals Melanoma-Derived Extracellular Vesicles: Focus on Their Proteome

Proteomes ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 21 ◽  
Author(s):  
Magdalena Surman ◽  
Ewa Stępień ◽  
Małgorzata Przybyło

Malignant melanoma is one of the most aggressive types of cancer, and its incidence is increasing rapidly each year. Despite the extensive research into improved diagnostic and treatment methods, early detection and disease constraint still present significant challenges. As successful isolation protocols have been developed, extracellular vesicles (EVs) have become the subject of extensive investigation in terms of their role in cancer progression and as a possible source of disease biomarkers. Besides functional studies, quantitative and qualitative proteomics have recently emerged as promising tools for the advancement of melanoma biomarkers. Nevertheless, the amount of data concerning the proteome of melanoma-derived EVs is still very limited. In this review we cover the current knowledge on protein content of melanoma-derived EVs, with a focus on their potential role in the development and progression of melanomas.

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.


2019 ◽  
Vol 20 (10) ◽  
pp. 2584 ◽  
Author(s):  
Shinsuke Kikuchi ◽  
Yusuke Yoshioka ◽  
Marta Prieto-Vila ◽  
Takahiro Ochiya

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.


2019 ◽  
Author(s):  
Javier Mariscal ◽  
Tatyana Vagner ◽  
Minhyung Kim ◽  
Bo Zhou ◽  
Andrew Chin ◽  
...  

AbstractExtracellular vesicles (EVs) are membrane-enclosed particles that play an important role in cancer progression and have emerged as a promising source of circulating biomarkers. Protein S-acylation, also known as palmitoylation, has been proposed as a post-translational mechanism that modulates the dynamics of EV biogenesis and protein cargo sorting. However, technical challenges have limited large-scale profiling of the whole palmitoyl-proteins of EVs. We successfully employed a novel approach that combines low-background acyl-biotinyl exchange (LB-ABE) with label-free proteomics to analyze the palmitoyl proteome of large EVs (L-EVs) and small EVs (S-EVs) from prostate cancer cells. Here we report the first palmitoyl-protein signature of EVs, and demonstrate that L- and S-EVs harbor proteins associated with distinct biological processes and subcellular origin. We identified STEAP1, STEAP2, and ABBC4 as prostate cancer-specific palmitoyl proteins enriched in both EV populations in comparison with the originating cell lines. Importantly, the presence of the above proteins in EVs was significantly reduced upon inhibition of palmitoylation in the producing cells. These results suggest that palmitoylation may be involved in the differential sorting of proteins to distinct EV populations and allow for better detection of disease biomarkers.


Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5669
Author(s):  
Akbar Lulu Marzan ◽  
Sarah Elizabeth Stewart

Pancreatic cancer is one of the deadliest cancers worldwide, with a 5-year survival rate of less than 10%. This dismal survival rate can be attributed to several factors including insufficient diagnostics, rapid metastasis and chemoresistance. To identify new treatment options for improved patient outcomes, it is crucial to investigate the underlying mechanisms that contribute to pancreatic cancer progression. Accumulating evidence suggests that extracellular vesicles, including exosomes and microvesicles, are critical players in pancreatic cancer progression and chemoresistance. In addition, extracellular vesicles also have the potential to serve as promising biomarkers, therapeutic targets and drug delivery tools for the treatment of pancreatic cancer. In this review, we aim to summarise the current knowledge on the role of extracellular vesicles in pancreatic cancer progression, metastasis, immunity, metabolic dysfunction and chemoresistance, and discuss their potential roles as biomarkers for early diagnosis and drug delivery vehicles for treatment of pancreatic cancer.


Author(s):  
Naoya Kuriyama ◽  
Yusuke Yoshioka ◽  
Shinsuke Kikuchi ◽  
Nobuyoshi Azuma ◽  
Takahiro Ochiya

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.


Membranes ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 453
Author(s):  
Víctor Acevedo-Sánchez ◽  
Ruth M. Rodríguez-Hernández ◽  
Sergio R. Aguilar-Ruíz ◽  
Honorio Torres-Aguilar ◽  
María de los A. Romero-Tlalolini

Since their description, extracellular vesicles (EVs) have shown growing relevance in cancer progression. These cell structures contain and transfer molecules such as nucleic acids (including DNA and RNA), proteins, and lipids. Despite the rising information about EVs’ relationship with cancer, there is still scarce evidence about their content and function in cervical cancer. Interestingly, the composition and purposes of some cellular molecules and the expression of oncogenic proteins packaged in EVs seem modified in HPV-infected cells; and, although only the E6 oncogenic protein has been detected in exosomes from HPV-positive cells, both E6/E7 oncogenes mRNA has been identified in EVs; however, their role still needs to be clarified. Given that EVs internalizing into adjacent or distant cells could modify their cellular behavior or promote cancer-associated events like apoptosis, proliferation, migration, or angiogenesis in receptor cells, their comprehensive study will reveal EV-associated mechanisms in cervical cancer. This review summarizes the current knowledge in composition and functions of cervical cancer and HPV Infection-derived EVs.


Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1733
Author(s):  
Marianna D’Anca ◽  
Chiara Fenoglio ◽  
Francesca Romana Buccellato ◽  
Caterina Visconte ◽  
Daniela Galimberti ◽  
...  

Although extracellular vesicles (EVs) were initially relegated to a waste disposal role, nowadays, they have gained multiple fundamental functions working as messengers in intercellular communication as well as exerting active roles in physiological and pathological processes. Accumulating evidence proves the involvement of EVs in many diseases, including those of the central nervous system (CNS), such as multiple sclerosis (MS). Indeed, these membrane-bound particles, produced in any type of cell, carry and release a vast range of bioactive molecules (nucleic acids, proteins, and lipids), conferring genotypic and phenotypic changes to the recipient cell. This means that not only EVs per se but their content, especially, could reveal new candidate disease biomarkers and/or therapeutic agents. This review is intended to provide an overview regarding current knowledge about EVs’ involvement in MS, analyzing the potential versatility of EVs as a new therapeutic tool and source of biomarkers.


2019 ◽  
Vol 2019 ◽  
pp. 1-19 ◽  
Author(s):  
Maria Concetta Cufaro ◽  
Damiana Pieragostino ◽  
Paola Lanuti ◽  
Claudia Rossi ◽  
Ilaria Cicalini ◽  
...  

Extracellular Vesicles (EVs) are small membrane-enclosed particles released by cells and able to vehiculate information between them. The term EVs categorizes many and different vesicles based on their biogenesis and release pathway, such as exosomes (Exo), ectosomes, or shedding microvesicles (SMVs), apoptotic blebs (ABs), and other EVs subsets, generating a heterogeneous group of components able to redistribute their cargo into the entire organism. Moreover EVs are becoming increasingly important in monitoring cancer progression and therapy, since they are able to carry specific disease biomarkers such as Glypican-1, colon cancer-associated transcript 2, CD63, CD24, and many others. The importance of their biological role together with their heterogeneity prompted researchers to adopt and standardize purification methods able to isolate EVs for characterizing their cargo. In this way, mass spectrometry (MS)-based proteomics approaches are emerging as promising tool for the identification and quantification of EVs protein cargoes, but this technique resulted to be deeply influenced by the low quality of the isolation techniques. This review presents the state-of-the-art of EVs isolation, purification, and characterization for omics studies, with a particular focus to their potential use in monitoring cancer progression and therapy.


2021 ◽  
Vol 11 ◽  
Author(s):  
Ying Zhang ◽  
Jin-Soo Kim ◽  
Tian-Zhen Wang ◽  
Robert U. Newton ◽  
Daniel A. Galvão ◽  
...  

Physical exercise is increasingly recognized as a valuable treatment strategy in managing prostate cancer, not only enhancing supportive care but potentially influencing disease outcomes. However, there are limited studies investigating mechanisms of the tumor-suppressive effect of exercise. Recently, extracellular vesicles (EVs) have been recognized as a therapeutic target for cancer as tumor-derived EVs have the potential to promote metastatic capacity by transferring oncogenic proteins, integrins, and microRNAs to other cells and EVs are also involved in developing drug resistance. Skeletal muscle has been identified as an endocrine organ, releasing EVs into the circulation, and levels of EV-containing factors have been shown to increase in response to exercise. Moreover, preclinical studies have demonstrated the tumor-suppressive effect of protein and microRNA contents in skeletal muscle-derived EVs in various cancers, including prostate cancer. Here we review current knowledge of the tumor-derived EVs in prostate cancer progression and metastasis, the role of exercise in skeletal muscle-derived EVs circulating levels and the alteration of their contents, and the potential tumor-suppressive effect of skeletal muscle-derived EV contents in prostate cancer. In addition, we review the proposed mechanism of exercise in the uptake of skeletal muscle-derived EVs in prostate cancer.


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