M2 Macrophage–Derived Exosomes Facilitate HCC Metastasis by Transferring αMβ2 Integrin to Tumor Cells. Issue 4 (13th April 2021)

• Record Type: Journal Article
• Authors: Wu, Jindao; Gao, Wen; Tang, Qiyun; Yu, Yue; You, Wei; Wu, Zhengshan; Fan, Ye; Zhang, Long; Wu, Chen; Han, Guoyong; Zuo, Xueliang; Zhang, Yao; Chen, Zhiqiang; Ding, Wenzhou; Li, Xiangcheng; Lin, Fengming; Shen, Hongbing; Tang, Jinhai; Zhang, Yaqin; Wang, Xuehao
• Is Part Of: Hepatology. Volume 73:Issue 4(2021)
• Page Start: 1365
• Page End: 1380
• Publication Date: 2021-04-13
• Subjects: Heart -- Diseases -- Nursing -- Periodicals; Lungs -- Diseases -- Nursing -- Periodicals; Intensive care nursing -- Periodicals; Foie -- Maladies -- Périodiques; 616.362
• DOI: 10.1002/hep.31432
• Languages: English
• ISSNs: 0270-9139

Abstract

Abstract : Background and Aims: The development and progression of hepatocellular carcinoma (HCC) is dependent on its local microenvironment. Tumor‐associated macrophages (TAMs) are deemed a key factor for the tumor microenvironment and attribute to contribute to tumor aggressiveness. However, the detailed mechanism underlying the pro‐metastatic effect of TAMs on HCC remains undefined. Approach and Results: The present study proved that TAMs were enriched in HCC. TAMs were characterized by an M2‐polarized phenotype and accelerated the migratory potential of HCC cells in vitro and in vivo . Furthermore, we found that M2‐derived exosomes induced TAM‐mediated pro‐migratory activity. With the use of mass spectrometry, we identified that integrin, αM β2 (CD11b/CD18), was notably specific and efficient in M2 macrophage–derived exosomes (M2 exos). Blocking either CD11b and/or CD18 elicited a significant decrease in M2 exos–mediated HCC cell metastasis. Mechanistically, M2 exos mediated an intercellular transfer of the CD11b/CD18, activating the matrix metalloproteinase‐9 signaling pathway in recipient HCC cells to support tumor migration. Conclusions: Collectively, the exosome‐mediated transfer of functional CD11b/CD18 protein from TAMs to tumor cells may have the potency to boost the migratory potential of HCC cells, thus providing insights into the mechanism of tumor metastasis.