Mitochondrial protein enriched extracellular vesicles discovered in human melanoma tissues can be detected in patient plasma

Jang, Su Chul; Crescitelli, Rossella; Cvjetkovic, Aleksander; Belgrano, Valerio; Bagge, Roger Olofsson; Sundfeldt, Karin; Ochiya, Takahiro; Kalluri, Raghu; Lötvall, Jan

doi:10.1080/20013078.2019.1635420

Cited by 132 publications

(147 citation statements)

References 51 publications

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“…EVs from patients with HTR disease contain full mitochondrial genome that might have been transferred to HTS/HTD cells to sustain oxidative phosphorylation, an exit from dormancy and the development of HTR disease (111). Additional findings show that EVs from melanoma, ovarian and breast cancer tissues contain mitochondrial membrane proteins and active mitochondrial enzymes that are not detected in healthy controls (112), thus corroborating the hypothesis that energy metabolism reprogramming in cancer cells may occur also via EVs.…”

Section: Implication Of Extracellular Vesicles and Damage-associated supporting

confidence: 64%

Extracellular Vesicles and Damage-Associated Molecular Patterns: A Pandora’s Box in Health and Disease

et al. 2020

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Sterile inflammation develops as part of an innate immunity response to molecules released upon tissue injury and collectively indicated as damage-associated molecular patterns (DAMPs). While coordinating the clearance of potential harmful stimuli, promotion of tissue repair, and restoration of tissue homeostasis, a hyper-activation of such an inflammatory response may be detrimental. The complex regulatory pathways modulating DAMPs generation and trafficking are actively investigated for their potential to provide relevant insights into physiological and pathological conditions. Abnormal circulating extracellular vesicles (EVs) stemming from altered endosomal-lysosomal system have also been reported in several age-related conditions, including cancer and neurodegeneration, and indicated as a promising route for therapeutic purposes. Along this pathway, mitochondria may dispose altered components to preserve organelle homeostasis. However, whether a common thread exists between DAMPs and EVs generation is yet to be clarified. A deeper understanding of the highly complex, dynamic, and variable intracellular and extracellular trafficking of DAMPs and EVs, including those of mitochondrial origin, is needed to unveil relevant pathogenic pathways and novel targets for drug development. Herein, we describe the mechanisms of generation of EVs and mitochondrial-derived vesicles along the endocytic pathway and discuss the involvement of the endosomal-lysosomal in cancer and neurodegeneration (i.e., Alzheimer’s and Parkinson’s disease).

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Section: Implication Of Extracellular Vesicles and Damage-associated supporting

confidence: 64%

Extracellular Vesicles and Damage-Associated Molecular Patterns: A Pandora’s Box in Health and Disease

et al. 2020

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“…More recently, Cresticelli et al [42] performed proteomic analysis of small and large EVs isolated from melanoma tumors and confirmed that metastatic melanoma tissues contain a mixture of EVs derived from tumor and immune cells. The same group also showed that two mitochondrial inner membrane proteins: cytochrome c oxidase subunit 2 (MT-CO2) and cytochrome c oxidase subunit 6C (COX6c) are enriched in the plasma of melanoma patients as well as in tumor tissues-derived EVs compared to healthy controls [43]. Studies using human tumor tissues are particularly valuable, since they fully reflect the complexity and cellular interactions present within the tumor microenvironment.…”

Section: Melanoma-derived Ectosomes As a Source Of Potential Disease mentioning

confidence: 99%

Mass Spectrometry-Based Proteomic Characterization of Cutaneous Melanoma Ectosomes Reveals the Presence of Cancer-Related Molecules

Surman

Kędracka–Krok

Hoja-Łukowicz

et al. 2020

IJMS

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Cutaneous melanoma (CM) is an aggressive type of skin cancer for which effective biomarkers are still needed. Recently, the protein content of extracellular vesicles (ectosomes and exosomes) became increasingly investigated in terms of its functional role in CM and as a source of novel biomarkers; however, the data concerning the proteome of CM-derived ectosomes is very limited. We used the shotgun nanoLC–MS/MS approach to the profile protein content of ectosomes from primary (WM115, WM793) and metastatic (WM266-4, WM1205Lu) CM cell lines. Additionally, the effect exerted by CM ectosomes on recipient cells was assessed in terms of cell proliferation (Alamar Blue assay) and migratory properties (wound healing assay). All cell lines secreted heterogeneous populations of ectosomes enriched in the common set of proteins. A total of 1507 unique proteins were identified, with many of them involved in cancer cell proliferation, migration, escape from apoptosis, epithelial–mesenchymal transition and angiogenesis. Isolated ectosomes increased proliferation and motility of recipient cells, likely due to the ectosomal transfer of different cancer-promoting molecules. Taken together, these results confirm the significant role of ectosomes in several biological processes leading to CM development and progression, and might be used as a starting point for further studies exploring their diagnostic and prognostic potential.

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“…In 2017, Vella et al used frozen human brain tissue to study EVs [31]. More recently, Jang et al studied EVs from metastatic human melanoma and Jingushi et al isolated EVs from human kidney tumors [21,32]. Although Jingushi et al reported successful EV isolation from RCC, we found it necessary to optimize available protocols to reduce non-EV contaminants to acceptable levels.…”

Section: Discussionmentioning

confidence: 95%

“…We have adapted an EV isolation method employed for metastatic melanoma and optimized it to isolate EVs from kidney tumor and normal kidney tissue [21]. This protocol demonstrates a high EV yield that is sufficient for downstream analysis.…”

Section: Introductionmentioning

confidence: 99%

Extracellular vesicle isolation from human renal cancer tissue

et al. 2020

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Renal cell carcinoma is a lethal disease that is often discovered incidentally. New non-invasive biomarkers are needed to aid diagnosis and treatment. Extracellular vesicles (EVs), membranous vesicles secreted by all cells, are a promising potential source for cancer biomarkers, but new methods are required that are both sensitive and specific for cancer identification. We have developed an EV isolation protocol optimized for kidney tumor and normal kidney tissue that yields a high vesicle concentration, confirmed by nanoparticle tracking analysis (NanoSight) and by nanoscale flow cytometry (NanoFCM). Using Western blot, we confirmed presence of EV markers CD81, CD63, flotillin-1, and absence of cellular debris, calnexin. Transmission electron microscopy images demonstrate intact membranous EVs. This new method improves existing protocols with additional steps to reduce contaminants in the EV product. Characterization of our isolation product confirms successful isolation of EVs with minimal contamination. The particle yields of our protocol are consistent and high as assessed by both standard and novel methods. This optimized protocol will contribute to biomarker discovery and biological studies of EVs in renal cancer.

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Mitochondrial protein enriched extracellular vesicles discovered in human melanoma tissues can be detected in patient plasma

Abstract: Lötvall (2019) Mitochondrial protein enriched extracellular vesicles discovered in human melanoma tissues can be detected in patient plasma,

Cited by 132 publications

References 51 publications

Extracellular Vesicles and Damage-Associated Molecular Patterns: A Pandora’s Box in Health and Disease

Extracellular Vesicles and Damage-Associated Molecular Patterns: A Pandora’s Box in Health and Disease

Mass Spectrometry-Based Proteomic Characterization of Cutaneous Melanoma Ectosomes Reveals the Presence of Cancer-Related Molecules

Extracellular vesicle isolation from human renal cancer tissue

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