Circulating extracellular vesicle‐associated CD163 and CD206 in multiple myeloma

Abstract

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.

Macrophage Activation Markers, CD163 and CD206, in Acute-on-Chronic Liver Failure

“…Additionally, we have presented data suggesting that CD206, like CD163, also exists in an extracellular vesicle-associated form (Unpublished data and [42]). Using ExoQuick™ as the means of EV-isolation, we were able to measure sCD206 in both the free protein and the EV-associated protein fraction.…”

“…This is in agreement with unpublished data from our group in which we find an increased fraction of EV-CD163 in patients suffering from chronic alcoholic liver cirrhosis, compared to patients with alcoholic hepatitis. Lastly, we have evaluated the distribution of CD163 fractions in multiple myeloma in which we observed an increased fraction of EV-CD163 in newly diagnosed multiple myeloma patients compared to patients with relapse and in remission [42].…”

Identification of six hub genes and analysis of their correlation with drug sensitivity in acute myeloid leukemia through bioinformatics

“…Its overexpression is associated with associated with a poor prognosis in AML and the immune/inflammatory response, which is potential biomarker of myeloid leukemia cutis (38,39). At the same time, CD163 is also involved in the development of multiple myeloma, meningioma, Hodgkin lymphoma and colorectal cancer (40)(41)(42)(43). Additionally, CD163 is regarded as a potential therapeutic target for cell-directed therapy on macrophages in some cancers, such as glioma, gastric cancer (44)(45)(46).…”

Clinical relevance of extracellular vesicles in hematological neoplasms: from liquid biopsy to cell biopsy

“…Furthermore, CD163 + EV level was higher in newly diagnosed MM as compared to relapsed patients. So, macrophage-associated EVs may have monitoring and prognostic biomarker potential in MM [51]. Furthermore, in newly diagnosed (n = 5) and relapsed (n = 4) MM patients' follow-up samples, after 2-3 months of treatment, no significant changes in CD163 + EV and CD206 + EV levels were observed compared to prior to treatment, while Ecto-CD163 and total sCD163 levels increased significantly during treatment [51].…”

“…So, macrophage-associated EVs may have monitoring and prognostic biomarker potential in MM [51]. Furthermore, in newly diagnosed (n = 5) and relapsed (n = 4) MM patients' follow-up samples, after 2-3 months of treatment, no significant changes in CD163 + EV and CD206 + EV levels were observed compared to prior to treatment, while Ecto-CD163 and total sCD163 levels increased significantly during treatment [51]. Although confirmation by survival studies with longer follow-up patients is needed, these data might suggest that Ecto-CD163 reflects acute inflammatory changes in macrophage activation, whereas CD163 + EV changes are regulated by other mechanisms.…”