Retracted: M2 Macrophage–Derived Exosomes Facilitate HCC Metastasis by Transferring αMβ2 Integrin to Tumor Cells

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, αMβ2 (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.

Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities

“…2 In addition, acceleration of the migratory potential of HCC cells is induced by TAM-derived α M β 2 (CD11/18)-containing exosomes, which have been reported to activate the MMP9 signaling pathway. 200 Through the production of various cytokines, including CCL17, CCL18, and CCL22, TAMs attract Tregs to the tumor environment, thereby hampering cytotoxic T cell activation and thus promoting tumor development. 201 Mouse models of hepatocarcinogenesis and observations of human tissues have indicated that macrophage subsets in the liver have stage-dependent effects.…”

Bisecting GlcNAc modification diminishes the pro‐metastatic functions of small extracellular vesicles from breast cancer cells

“…Many recent studies have shown that sEVs function as carriers to transport functional materials (proteins, mRNAs, microRNAs, lncRNAs) to recipient cells, and modulate recipient cell behaviour. For example, vesicular EGFR (Zhang et al., 2017), annexin A6 (ANXA6) (Keklikoglou et al., 2019) and integrin αMβ2 (Wu et al., 2020) were reported to facilitate the metastasis of recipient cells. On the other hand, several sEV cargos, were documented to suppress the cancer migration of recipient cells.…”

The Role of Tumor Associated Macrophages in Hepatocellular Carcinoma

“…Wu et al . recently manifested that CD11b/CD18, as well as integrin, which derived from M2 macrophage exosomes, had the potency to boost the migratory potential of HCC cells 73 . Additionally, HCC cell-derived Wnt ligands stimulate M2 polarization of TAMs, which reversely result in tumor growth, metastasis and immunosuppression in HCC 74 .…”