Dataset Information

M2 Macrophage-Derived Exosomes Facilitate HCC Metastasis by Transferring α_M β₂ 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, α_M 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.

SUBMITTER: Wu J

PROVIDER: S-EPMC8360085 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Publications

M2 Macrophage-Derived Exosomes Facilitate HCC Metastasis by Transferring α<sub>M</sub> β<sub>2</sub> Integrin to Tumor Cells.

Wu Jindao J Gao Wen W Tang Qiyun Q Yu Yue Y You Wei W Wu Zhengshan Z Fan Ye Y Zhang Long L Wu Chen C Han Guoyong G Zuo Xueliang X Zhang Yao Y Chen Zhiqiang Z Ding Wenzhou W Li Xiangcheng X Lin Fengming F Shen Hongbing H Tang Jinhai J Zhang Yaqin Y Wang Xuehao X

Hepatology (Baltimore, Md.) 20210401 4

<h4>Background and aims</h4>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.<h4>Approach and results</h4>The present study proved that TAMs were enriched in HCC. TAMs were characterized by an ...[more]

PMID: 32594528

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Project description:BackgroundTo overcome the hostile hypoxic microenvironment of solid tumors, tumor cells secrete a large number of non-coding RNA-containing exosomes that facilitate tumor development and metastasis. However, the precise mechanisms of tumor cell-derived exosomes during hypoxia are unknown. Here, we aim to clarify whether hypoxia affects tumor growth and progression by transferring long non-coding RNA-urothelial cancer-associated 1 (lncRNA-UCA1) enriched exosomes secreted from bladder cancer cells.MethodsWe used bladder cancer 5637 cells with high expression of lncRNA-UCA1 as exosome-generating cells and bladder cancer UMUC2 cells with low expression of lncRNA-UCA1 as recipient cells. Exosomes derived from 5637 cells cultured under normoxic or hypoxic conditions were isolated and identified by transmission electron microscopy, nanoparticle tracking analysis and western blotting analysis. These exosomes were co-cultured with UMUC2 cells to evaluate cell proliferation, migration and invasion. We further investigated the roles of exosomal lncRNA-UCA1 derived from hypoxic 5637 cells by xenograft models. The availability of lncRNA-UCA1 in serum-derived exosomes as a biomarker for bladder cancer was also assessed.ResultsWe found that hypoxic exosomes derived from 5637 cells promoted cell proliferation, migration and invasion, and hypoxic exosomal RNAs could be internalized by three bladder cancer cell lines. Importantly, lncRNA-UCA1 was secreted in hypoxic 5637 cell-derived exosomes. Compared with normoxic exosomes, hypoxic exosomes derived from 5637 cells showed the higher expression levels of lncRNA-UCA1. Moreover, Hypoxic exosomal lncRNA-UCA1 could promote tumor growth and progression though epithelial-mesenchymal transition, in vitro and in vivo. In addition, the expression levels of lncRNA-UCA1 in the human serum-derived exosomes of bladder cancer patients were higher than that in the healthy controls.ConclusionTogether, our results demonstrate that hypoxic bladder cancer cells remodel tumor microenvironment to facilitate tumor growth and development though secreting the oncogenic lncRNA-UCA1-enriched exosomes and exosomal lncRNA-UCA1 in human serum has the possibility as a diagnostic biomarker for bladder cancer.

Dataset Information

M2 Macrophage-Derived Exosomes Facilitate HCC Metastasis by Transferring α_M β₂ Integrin to Tumor Cells.

Background and aims

Approach and results

Conclusions

Publications

M2 Macrophage-Derived Exosomes Facilitate HCC Metastasis by Transferring α<sub>M</sub> β<sub>2</sub> Integrin to Tumor Cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

M2 Macrophage-Derived Exosomes Facilitate HCC Metastasis by Transferring αM β2 Integrin to Tumor Cells.

Background and aims

Approach and results

Conclusions

Publications

M2 Macrophage-Derived Exosomes Facilitate HCC Metastasis by Transferring α<sub>M</sub> β<sub>2</sub> Integrin to Tumor Cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

M2 Macrophage-Derived Exosomes Facilitate HCC Metastasis by Transferring α_M β₂ Integrin to Tumor Cells.