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19.10.2018 | Original Article

INT-HA induces M2-like macrophage differentiation of human monocytes via TLR4-miR-935 pathway

Zeitschrift:
Cancer Immunology, Immunotherapy
Autoren:
Boke Zhang, Yan Du, Yiqing He, Yiwen Liu, Guoliang Zhang, Cuixia Yang, Feng Gao
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s00262-018-2261-6) contains supplementary material, which is available to authorized users.
Boke Zhang and Yan Du are co-first authors.

Abstract

As a major component of the microenvironment of solid tumors, tumor-associated macrophages (TAMs) facilitate tumor progression. Intermediate-sized hyaluronan (INT-HA) fragments have an immunological function in cell differentiation; however, their role in promoting the polarization of non-activated macrophages to an M2-like TAM phenotype has not been characterized, and the underlying mechanisms remain unclear. Here, we used a miRNA microarray to find that some miRNAs (especially miR-935) were differentially regulated in INT-HA-induced M2-like macrophages. According to RT-qPCR and Western blot, there was an association between miR-935 and C/EBPβ, that control the polarization of macrophages. Moreover, we found that INT-HA induced an M2-like phenotype via the TLR4 receptor. In our study, there was a negative correlation between plasma HA and miR-935 in monocytes from the peripheral blood of patients with solid tumors. There was also a negative correlation between miR-935 and M2-like macrophage markers in monocytes. These findings suggest that HA fragments interact with TLR4 and educate macrophage polarization to an M2-like phenotype via miR-935. Therefore, this study provides new insight into the role of miR-935 in INT-HA-induced M2-like polarization, and suggests a potential therapeutic target for antitumor treatment.

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Zusatzmaterial
Supplementary material 1 (PDF 468 KB)
262_2018_2261_MOESM1_ESM.pdf
Literatur
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