Top

Published in:

01-02-2019 | Original Article

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

Authors: Boke Zhang, Yan Du, Yiqing He, Yiwen Liu, Guoliang Zhang, Cuixia Yang, Feng Gao

Published in: Cancer Immunology, Immunotherapy | Issue 2/2019

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.

Available only for authorised users

Italiani P, Boraschi D (2014) From monocytes to M1/M2 macrophages: phenotypical vs. functional differentiation. Front Immunol 5:514. https://doi.org/10.3389/fimmu.2014.00514 CrossRefPubMedPubMedCentral

Ruffell B, Affara NI, Coussens LM (2012) Differential macrophage programming in the tumor microenvironment. Trends Immunol 33:119–126. https://doi.org/10.1016/j.it.2011.12.001 CrossRefPubMedPubMedCentral

Cook J, Hagemann T (2013) Tumour-associated macrophages and cancer. Curr Opin Pharmacol 13:595–601. https://doi.org/10.1016/j.coph.2013.05.017 CrossRefPubMed

Spinelli FM, Vitale DL, Demarchi G et al (2015) The immunological effect of hyaluronan in tumor angiogenesis. Clin Transl Immunol 4:e52. https://doi.org/10.1038/cti.2015.35 CrossRef

Stern R, Asari AA, Sugahara KN (2006) Hyaluronan fragments: an information-rich system. Eur J Cell Biol 85:699–715. https://doi.org/10.1016/j.ejcb.2006.05.009 CrossRefPubMed

Misra S, Hascall VC, Markwald RR et al (2015) Interactions between hyaluronan and its receptors (CD44, RHAMM) regulate the activities of inflammation and cancer. Front Immunol 6:201. https://doi.org/10.3389/fimmu.2015.00201 CrossRefPubMedPubMedCentral

Laurent TC, Laurent UB, Fraser JR (1995) Functions of hyaluronan. Ann Rheum Dis 54:429–432CrossRefPubMedPubMedCentral

Tian X, Azpurua J, Hine C et al (2013) High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat. Nature 499:346–349. https://doi.org/10.1038/nature12234 CrossRefPubMedPubMedCentral

Termeer CC, Hennies J, Voith U et al (2000) Oligosaccharides of hyaluronan are potent activators of dendritic cells. J Immunol 165:1863–1870CrossRefPubMed

10.

Horton MR, Shapiro S, Bao C et al (1999) Induction and regulation of macrophage metalloelastase by hyaluronan fragments in mouse macrophages. J Immunol 162:4171–4176PubMed

11.

Termeer C, Benedix F, Sleeman J et al (2002) Oligosaccharides of Hyaluronan activate dendritic cells via toll-like receptor 4. J Exp Med 195:99–111CrossRefPubMedPubMedCentral

12.

Ponta H, Sherman L, Herrlich PA (2003) CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol 4:33–45. https://doi.org/10.1038/nrm1004 CrossRefPubMed

13.

Lawrence T, Natoli G (2011) Transcriptional regulation of macrophage polarization: enabling diversity with identity. Nat Rev Immunol 11:750–761. https://doi.org/10.1038/nri3088 CrossRefPubMed

14.

Kuang DM, Wu Y, Chen N et al (2007) Tumor-derived hyaluronan induces formation of immunosuppressive macrophages through transient early activation of monocytes. Blood 110:587–595. https://doi.org/10.1182/blood-2007-01-068031 CrossRefPubMed

15.

Rayahin JE, Buhrman JS, Zhang Y et al (2015) High and low molecular weight hyaluronic acid differentially influence macrophage activation. ACS Biomater Sci Eng 1:481–493. https://doi.org/10.1021/acsbiomaterials.5b00181 CrossRefPubMedPubMedCentral

16.

Weigel PH, Baggenstoss BA (2017) What is special about 200 kDa hyaluronan that activates hyaluronan receptor signaling? Glycobiology 27:868–877. https://doi.org/10.1093/glycob/cwx039 CrossRefPubMedPubMedCentral

17.

Sokolowska M, Chen LY, Eberlein M et al (2014) Low molecular weight hyaluronan activates cytosolic phospholipase A2alpha and eicosanoid production in monocytes and macrophages. J Biol Chem 289:4470–4488. https://doi.org/10.1074/jbc.M113.515106 CrossRefPubMed

18.

Yamawaki H, Hirohata S, Miyoshi T et al (2009) Hyaluronan receptors involved in cytokine induction in monocytes. Glycobiology 19:83–92. https://doi.org/10.1093/glycob/cwn109 CrossRefPubMed

19.

Gordon S, Martinez FO (2010) Alternative activation of macrophages: mechanism and functions. Immunity 32:593–604. https://doi.org/10.1016/j.immuni.2010.05.007 CrossRefPubMed

20.

Ruffell D, Mourkioti F, Gambardella A et al (2009) A CREB-C/EBPbeta cascade induces M2 macrophage-specific gene expression and promotes muscle injury repair. Proc Natl Acad Sci USA 106:17475–17480. https://doi.org/10.1073/pnas.0908641106 CrossRefPubMedPubMedCentral

21.

Cho IJ, Woo NR, Kim SG (2008) The identification of C/EBPbeta as a transcription factor necessary for the induction of MAPK phosphatase-1 by toll-like receptor-4 ligand. Arch Biochem Biophys 479:88–96. https://doi.org/10.1016/j.abb.2008.08.007 CrossRefPubMed

22.

Zhou D, Huang C, Lin Z et al (2014) Macrophage polarization and function with emphasis on the evolving roles of coordinated regulation of cellular signaling pathways. Cell Signal 26:192–197. https://doi.org/10.1016/j.cellsig.2013.11.004 CrossRefPubMed

23.

Squadrito ML, Etzrodt M, De Palma M et al (2013) MicroRNA-mediated control of macrophages and its implications for cancer. Trends Immunol 34:350–359. https://doi.org/10.1016/j.it.2013.02.003 CrossRefPubMedPubMedCentral

24.

Graff JW, Dickson AM, Clay G et al (2012) Identifying functional microRNAs in macrophages with polarized phenotypes. J Biol Chem 287:21816–21825. https://doi.org/10.1074/jbc.M111.327031 CrossRefPubMedPubMedCentral

25.

Cai X, Yin Y, Li N et al (2012) Re-polarization of tumor-associated macrophages to pro-inflammatory M1 macrophages by microRNA-155. J Mol Cell Biol 4:341–343. https://doi.org/10.1093/jmcb/mjs044 CrossRefPubMed

26.

Su S, Zhao Q, He C et al (2015) miR-142-5p and miR-130a-3p are regulated by IL-4 and IL-13 and control profibrogenic macrophage program. Nat Commun 6:8523. https://doi.org/10.1038/ncomms9523 CrossRefPubMed

27.

Squadrito ML, Pucci F, Magri L et al (2012) miR-511-3p modulates genetic programs of tumor-associated macrophages. Cell Rep 1:141–154. https://doi.org/10.1016/j.celrep.2011.12.005 CrossRefPubMed

28.

Banerjee S, Xie N, Cui H et al (2013) MicroRNA let-7c regulates macrophage polarization. J Immunol 190:6542–6549. https://doi.org/10.4049/jimmunol.1202496 CrossRefPubMed

29.

Maharjan AS, Pilling D, Gomer RH (2011) High and low molecular weight hyaluronic acid differentially regulate human fibrocyte differentiation. PLoS One 6:e26078. https://doi.org/10.1371/journal.pone.0026078 CrossRefPubMedPubMedCentral

30.

Zhang G, Guo L, Yang C et al (2016) A novel role of breast cancer-derived hyaluronan on inducement of M2-like tumor-associated macrophages formation. Oncoimmunology 5:e1172154. https://doi.org/10.1080/2162402X.2016.1172154 CrossRefPubMedPubMedCentral

31.

Eigsti RL, Sudan B, Wilson ME et al (2014) Regulation of activation-associated microRNA accumulation rates during monocyte-to-macrophage differentiation. J Biol Chem 289:28433–28447. https://doi.org/10.1074/jbc.M114.599316 CrossRefPubMedPubMedCentral

32.

Baer C, Squadrito ML, Laoui D et al (2016) Suppression of microRNA activity amplifies IFN-gamma-induced macrophage activation and promotes anti-tumour immunity. Nat Cell Biol. https://doi.org/10.1038/ncb3371 CrossRefPubMed

33.

Yan C, Yu J, Kang W et al (2016) miR-935 suppresses gastric signet ring cell carcinoma tumorigenesis by targeting Notch1 expression. Biochem Biophys Res Commun 470:68–74. https://doi.org/10.1016/j.bbrc.2015.12.116 CrossRefPubMed

34.

Yang M, Cui G, Ding M et al (2016) miR-935 promotes gastric cancer cell proliferation by targeting SOX7. Biomed Pharmacother 79:153–158. https://doi.org/10.1016/j.biopha.2016.01.011 CrossRefPubMed

35.

Liu X, Li J, Yu Z et al (2017) miR-935 Promotes Liver Cancer Cell Proliferation and Migration by Targeting SOX7. Oncol Res 25:427–435. https://doi.org/10.3727/096504016X14747300207374 CrossRefPubMedPubMedCentral

36.

Carter JV, Galbraith NJ, Yang D et al (2017) Blood-based microRNAs as biomarkers for the diagnosis of colorectal cancer: a systematic review and meta-analysis. Br J Cancer 116:762–774. https://doi.org/10.1038/bjc.2017.12 CrossRefPubMedPubMedCentral

37.

Chauhan R, Lahiri N (2016) Tissue- and serum-associated biomarkers of hepatocellular carcinoma. Biomark Cancer 8:37–55. https://doi.org/10.4137/BIC.S34413 CrossRefPubMedPubMedCentral

38.

Nakamura K, Sawada K, Yoshimura A et al (2016) Clinical relevance of circulating cell-free microRNAs in ovarian cancer. Mol Cancer 15:48. https://doi.org/10.1186/s12943-016-0536-0 CrossRefPubMedPubMedCentral

Title: INT-HA induces M2-like macrophage differentiation of human monocytes via TLR4-miR-935 pathway
Authors: Boke Zhang
Yan Du
Yiqing He
Yiwen Liu
Guoliang Zhang
Cuixia Yang
Feng Gao
Publication date: 01-02-2019
Publisher: Springer Berlin Heidelberg
Published in: Cancer Immunology, Immunotherapy / Issue 2/2019
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-018-2261-6

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2019

Hyperresponsiveness to interferon gamma exposure as a response mechanism to anti-PD-1 therapy in microsatellite instability colorectal cancer

Development of CDX-1140, an agonist CD40 antibody for cancer immunotherapy

The nature of the human T cell response to the cancer antigen 5T4 is determined by the balance of regulatory and inflammatory T cells of the same antigen-specificity: implications for vaccine design

Phase 1 study of everolimus and low-dose oral cyclophosphamide in patients with metastatic renal cell carcinoma

Upregulation of tumor PD-L1 by neoadjuvant chemoradiotherapy (neoCRT) confers improved survival in patients with lymph node metastasis of locally advanced rectal cancers

Tumor-infiltrating immune cell subpopulations and programmed death ligand 1 (PD-L1) expression associated with clinicopathological and prognostic parameters in ependymoma

Keynote webinar | Spotlight on antibody–drug conjugates in cancer