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Eur J Haematol ; 104(5): 409-419, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31855290

RESUMO

OBJECTIVES: Extracellular vesicles (EVs) are important for intercellular signalling in cancer. Tumour-associated macrophages, expressing the haemoglobin-haptoglobin and mannose receptors CD163 and CD206, are crucial for cancer progression. We recently identified CD163 on EVs in the circulation as a fraction of total soluble CD163 (sCD163). Here, we investigated the presence of CD163 and CD206-positive EVs (EV-CD163, EV-CD206) in patients with multiple myeloma (MM). METHODS: We enrolled patients with MM (n = 32), monoclonal gammopathy of undetermined significance (MGUS) (n = 8) and healthy donors (n = 16). Plasma protein levels were determined by ELISA before and after vesicle precipitation. Monocytes were examined by flow cytometry, and leucocyte CD163 mRNA by qPCR. RESULTS: Fractions of EV-CD163 and EV-CD206 were significantly elevated in patients with newly diagnosed MM (median = 39.8%, 76.5%, respectively) compared to patients with relapse (15.6%, P = .02, 42.5%, P = .003), remission (16.9%, P < .0001, 25.2%, P < .0001), MGUS (17.8%, P < .01, 33.1%, P = .0005) and healthy donors (14.8%, P < .0001, 35.5%, P < .0001). Whole blood CD163 mRNA did not vary between the groups. The intermediate monocyte subset showed a higher CD163 expression in newly diagnosed patients. CONCLUSIONS: Our results indicate that macrophage-derived EVs may play a role in the late phase of malignant progression of MM, and encourage further EV investigations in functional experiments.


Assuntos
Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Vesículas Extracelulares/metabolismo , Glicoproteínas de Membrana/metabolismo , Mieloma Múltiplo/metabolismo , Receptores de Superfície Celular/metabolismo , Receptores Imunológicos/metabolismo , Idoso , Antígenos CD/genética , Antígenos de Diferenciação Mielomonocítica/genética , Biomarcadores , Proteínas Sanguíneas , Estudos de Casos e Controles , Feminino , Citometria de Fluxo , Expressão Gênica , Humanos , Masculino , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Gamopatia Monoclonal de Significância Indeterminada/sangue , Gamopatia Monoclonal de Significância Indeterminada/metabolismo , Mieloma Múltiplo/sangue , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genética , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , RNA Mensageiro/genética , Receptores de Superfície Celular/genética , Receptores Imunológicos/genética
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