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1.
Int J Mol Sci ; 23(22)2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36430925

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy. Tumor-derived exosomes (TEX) have immunoregulatory properties. Adenosine triphosphate (ATP) and its immunosuppressive precursor adenosine (ADO) have been found in cancerous tissue. We investigated the effect of TEX on B cells in the presence of ATP. TEX were isolated from human HNSCC cell line (PCI-13) cultures and co-cultured with peripheral blood B cells of healthy donors, with or without TEX in different concentrations and with or without a low (20 µM) or high (2000 µM) ATP dose. We were able to demonstrate that TEX inhibit B-cell proliferation. The addition of TEX to either ATP concentration showed a decreasing trend in CD39 expression on B cells in a dose-dependent manner. High ATP levels (2000 µM) increased apoptosis and necrosis, and analysis of apoptosis-associated proteins revealed dose-dependent effects of ATP, which were modified by TEX. Altogether, TEX exhibited dual immunomodulatory effects on B cells. TEX were immunosuppressive by inhibiting B-cell proliferation; they were immunostimulatory by downregulating CD39 expression. Furthermore, TEX were able to modulate the expression of pro- and anti-apoptotic proteins. In conclusion, our data indicate that TEX play an important, but complex, role in the tumor microenvironment.


Assuntos
Exossomos , Neoplasias de Cabeça e Pescoço , Intervenção Coronária Percutânea , Humanos , Exossomos/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Trifosfato de Adenosina/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Microambiente Tumoral
2.
Int J Mol Sci ; 22(7)2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33808435

RESUMO

Glioblastomas are among the most aggressive tumors, and with low survival rates. They are characterized by the ability to create a highly immunosuppressive tumor microenvironment. Exosomes, small extracellular vesicles (EVs), mediate intercellular communication in the tumor microenvironment by transporting various biomolecules (RNA, DNA, proteins, and lipids), therefore playing a prominent role in tumor proliferation, differentiation, metastasis, and resistance to chemotherapy or radiation. Exosomes are found in all body fluids and can cross the blood-brain barrier due to their nanoscale size. Recent studies have highlighted the multiple influences of tumor-derived exosomes on immune cells. Owing to their structural and functional properties, exosomes can be an important instrument for gaining a better molecular understanding of tumors. Furthermore, they qualify not only as diagnostic and prognostic markers, but also as tools in therapies specifically targeting aggressive tumor cells, like glioblastomas.


Assuntos
Exossomos/metabolismo , Exossomos/fisiologia , Glioblastoma/imunologia , Comunicação Celular/fisiologia , Exossomos/imunologia , Vesículas Extracelulares/imunologia , Vesículas Extracelulares/metabolismo , Glioblastoma/metabolismo , Humanos , Fatores Imunológicos/imunologia , Fatores Imunológicos/metabolismo , Imunomodulação/imunologia , Imunomodulação/fisiologia , Neoplasias/metabolismo , Microambiente Tumoral/fisiologia
3.
Artigo em Inglês | MEDLINE | ID: mdl-32024796

RESUMO

OBJECTIVE: To assess whether serum concentrations of the anti-inflammatory cytokine growth differentiation factor 15 (GDF-15) differ in patients with highly active multiple sclerosis (MS) vs patients with stable MS and healthy controls (HCs). METHODS: GDF-15 concentrations were measured by ELISA in serum and CSF in a cross-sectional cohort of patients with MS, patients with other inflammatory neurologic diseases (OIND), patients with noninflammatory neurologic diseases (NIND), and healthy controls (HC). Serum GDF-15 concentrations were measured in a longitudinally sampled cohort of clinically and radiologically well-characterized patients with MS and corresponding controls. RESULTS: Cross-sectionally measured median serum GDF-15 concentrations were significantly higher in patients with OIND (n = 42) (600 pg/mL, interquartile range [IQR] = 320-907 pg/mL) compared with HCs (n = 29) (325 pg/mL, IQR = 275-419 pg/mL; p = 0.0007), patients with NIND (n = 46) (304 pg/mL, IQR = 245-493 pg/mL; p = 0.0002), or relapsing MS (n = 42) (356 pg/mL, IQR = 246-460 pg/mL; p = 0.0002). CSF and serum concentrations of GDF-15 were correlated (r = 0.41, 95% CI = 0.25-0.56, p < 0.0001). In a longitudinally sampled cohort of patients with MS (n = 48), deeply phenotyped with quantitative clinical and MRI assessments, mean GDF-15 concentrations were significantly higher in patients with a stable disease course (405 pg/mL, SD = 202) than in patients with intermittent MRI activity (333 pg/mL, SD = 116; p = 0.02). CONCLUSIONS: Serum GDF-15 concentrations are increased in patients with MS with a stable disease course. These data suggest that GDF-15 may serve as a biomarker for disease stability in MS.


Assuntos
Progressão da Doença , Fator 15 de Diferenciação de Crescimento/sangue , Esclerose Múltipla/sangue , Esclerose Múltipla/fisiopatologia , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Estudos Transversais , Feminino , Fator 15 de Diferenciação de Crescimento/líquido cefalorraquidiano , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/diagnóstico por imagem , Adulto Jovem
4.
PLoS One ; 13(6): e0198029, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29933376

RESUMO

Exosomes are nanovesicles involved in intercellular communications. They are released by a variety of cell types; however, their presence in the inner ear has not been described in the literature. The aims of this study were to determine if exosomes are present in the inner ear and, if present, characterize the changes in their protein content in response to ototoxic stress. In this laboratory investigation, inner ear explants of 5-day-old Wistar rats were cultured and treated with either cisplatin or gentamicin. Hair cell damage was assessed by confocal microscopy. Exosomes were isolated using ExoQuick, serial centrifugation, and mini-column methods. Confirmation and characterization of exosomes was carried out using transmission electron microscopy (TEM), ZetaView, BCA protein analysis, and proteomics. Vesicles with a typical size distribution for exosomes were observed using TEM and ZetaView. Proteomic analysis detected typical exosome markers and markers for the organ of Corti. There was a statistically significant reduction in the exosome protein level and number of particles per cubic centimeter when the samples were exposed to ototoxic stress. Proteomic analysis also detected clear differences in protein expression when ototoxic medications were introduced. Significant changes in the proteomes of the exosomes were previously described in the context of hearing loss and ototoxic treatment. This is the first report describing exosomes derived from the inner ear. These findings may present an opportunity to conduct further studies with the hope of using exosomes as a biomarker to monitor inner ear function in the future.


Assuntos
Orelha Interna/citologia , Exossomos/metabolismo , Animais , Biomarcadores/metabolismo , Orelha Interna/efeitos dos fármacos , Exossomos/efeitos dos fármacos , Proteômica , Ratos , Ratos Wistar , Estresse Fisiológico/efeitos dos fármacos
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