Myeloid cell-expressed MNDA enhances M2 polarization to facilitate the metastasis of hepatocellular carcinoma

Meng, Yanru; Zhang, Mengxin; Li, Xinli; Wang, Xinxin; Dong, Qian; Zhang, Hu; Zhai, Yuanjun; Song, Qin; He, Fuchu; Tian, Chunyan; Sun, Aihua

doi:10.7150/ijbs.91877

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Int J Biol Sci 2024; 20(8):2814-2832. doi:10.7150/ijbs.91877 This issue Cite

Research Paper

Myeloid cell-expressed MNDA enhances M2 polarization to facilitate the metastasis of hepatocellular carcinoma

Yanru Meng^1,#, Mengxin Zhang^2,#, Xinli Li^2,#, Xinxin Wang⁴, Qian Dong², Hu Zhang², Yuanjun Zhai², Qin Song⁵, Fuchu He^1,2,3✉, Chunyan Tian^2,3,5✉, Aihua Sun^2,3,5✉

1. Department of Immunology, Medical College of Qingdao University, Qingdao, Shandong 266071, China.
2. State Key Laboratory of Proteomics, National Center for Protein Sciences (Beijing), Beijing Proteome Research Center, Beijing Institute of Lifeomics, Beijing 102206, China.
3. Research Unit of Proteomics Dirven Cancer Precision Medicine, Chinese Academy of Medical Sciences, Beijing, China.
4. Department of Pathology, Beijing You'an Hospital, Capital Medical University, Beijing 100069, China.
5. College of Life Sciences, Hebei University, Baoding 071002, Hebei, China.
^# These authors contributed equally to this work.

Citation:

Meng Y, Zhang M, Li X, Wang X, Dong Q, Zhang H, Zhai Y, Song Q, He F, Tian C, Sun A. Myeloid cell-expressed MNDA enhances M2 polarization to facilitate the metastasis of hepatocellular carcinoma. Int J Biol Sci 2024; 20(8):2814-2832. doi:10.7150/ijbs.91877. https://www.ijbs.com/v20p2814.htm

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Abstract

Stable infiltration of myeloid cells, especially tumor-associated M2 macrophages, acts as one of the essential features of the tumor immune microenvironment by promoting the malignant progression of hepatocellular carcinoma (HCC). However, the factors affecting the infiltration of M2 macrophages are not fully understood. In this study, we found the molecular subtypes of HCC with the worst prognosis are characterized by immune disorders dominated by myeloid cell infiltration. Myeloid cell nuclear differentiation antigen (MNDA) was significantly elevated in the most aggressive subtype and exhibited a positively correlation with M2 infiltration and HCC metastasis. Moreover, MNDA functioned as an independent prognostic predictor and has a good synergistic effect with some existing prognostic clinical indicators. We further confirmed that MNDA was primarily expressed in tumor M2 macrophages and contributed to the enhancement of its polarization by upregulating the expression of the M2 polarization enhancers. Furthermore, MNDA could drive the secretion of M2 macrophage-derived pro-metastasis proteins to accelerate HCC cells metastasis both in vivo and in vitro. In summary, MNDA exerts a protumor role by promoting M2 macrophages polarization and HCC metastasis, and can serve as a potential biomarker and therapeutic target for HCC.

Keywords: MNDA, HCC, metastasis, M2 polarization, exosome

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APA

Meng, Y., Zhang, M., Li, X., Wang, X., Dong, Q., Zhang, H., Zhai, Y., Song, Q., He, F., Tian, C., Sun, A. (2024). Myeloid cell-expressed MNDA enhances M2 polarization to facilitate the metastasis of hepatocellular carcinoma. International Journal of Biological Sciences, 20(8), 2814-2832. https://doi.org/10.7150/ijbs.91877.

ACS

Meng, Y.; Zhang, M.; Li, X.; Wang, X.; Dong, Q.; Zhang, H.; Zhai, Y.; Song, Q.; He, F.; Tian, C.; Sun, A. Myeloid cell-expressed MNDA enhances M2 polarization to facilitate the metastasis of hepatocellular carcinoma. Int. J. Biol. Sci. 2024, 20 (8), 2814-2832. DOI: 10.7150/ijbs.91877.

NLM

CSE

Meng Y, Zhang M, Li X, Wang X, Dong Q, Zhang H, Zhai Y, Song Q, He F, Tian C, Sun A. 2024. Myeloid cell-expressed MNDA enhances M2 polarization to facilitate the metastasis of hepatocellular carcinoma. Int J Biol Sci. 20(8):2814-2832.

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