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Cited by 381Extracellular vesicles in diseaseImmune cells in cancerCancer Cells and Metastasis

Tumor-associated macrophages-derived exosomes promote the migration of gastric cancer cells by transfer of functional Apolipoprotein E

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Zheng, Peiming, Luo, Qin, Wang, Weiwei, Li, Junhua, Wang, Tingting, Wang, Ping, Chen, Lei, Zhang, Peng +8 more·2018·Cell Death & Disease
DOI 10.1038/s41419-018-0465-5PMC PMC5864742
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Abstract

Tumor-associated macrophages (TAMs) are a major component of the tumor microenvironment and have been shown to contribute to tumor aggressiveness. However, the detailed mechanisms underlying the pro-metastatic effect of TAMs on gastric cancer are not clearly defined. Here, we show that TAMs are enriched in gastric cancer. TAMs are characterized by M2-polarized phenotype and promote migration of gastric cancer cells in vitro and in vivo. Furthermore, we find that M2-derived exosomes determine the TAMs-mediated pro-migratory activity. Using mass spectrometry, we identify that apolipoprotein E (ApoE) is highly specific and effective protein in M2 macrophages-derived exosomes. Moreover, TAMs are uniquely immune cells population expressed ApoE in gastric cancer microenvironment. However, exosomes derived from M2 macrophages of Apoe −/− mice have no significant effect on the migration of gastric cancer cells in vitro and in vivo. Mechanistically, M2 macrophage-derived exosomes mediate an intercellular transfer of ApoE-activating PI3K-Akt signaling pathway in recipient gastric cancer cells to remodel the cytoskeleton-supporting migration. Collectively, our findings signify that the exosome-mediated transfer of functional ApoE protein from TAMs to the tumor cells promotes the migration of gastric cancer cells.

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  • Macrophage-derived ApoE promotes tumorigenesis either through inducing the expression of Cxcl1 and Cxcl5 in pancreatic ductal adenocarcinoma cells, or activating PI3K-AKT signaling pathway in recipient gastric cancer cells.

    “Macrophage-derived ApoE promotes tumorigenesis either through inducing the expression of Cxcl1 and Cxcl5 in pancreatic ductal adenocarcinoma cells [73], or activating PI3K-AKT signaling pathway in recipient gastric cancer cells [75].”

    From Single-cell transcriptome reveals the reprogramming of immune microenvironment during the transition from MASH to HCC (2025) · cites this paper as [75]

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References 49 · Cited by 381

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Authors
Zheng, P., Luo, Q., Wang, W., Li, J., Wang, T., Wang, P., Chen, L., Zhang, P., Chen, H., Liu, Y., Dong, P., Xie, G., Ma, Y., Jiang, L., Yuan, X., & Shen, L.
Affiliations
Shanghai Jiao Tong University (CN)
Corresponding author
  • Yuan, Xiangliang
  • Shen, Lisong
ORCID
Venue
Cell Death & Disease
Publisher
Springer Science and Business Media LLC
Published
2018-03-22
Volume
9
Issue
4
Pages
434-434
ISSN
2041-4889 (ISSN-L)
DOI
10.1038/s41419-018-0465-5
PMC
PMC5864742
OpenAlex
W2790358993
Cited by
381
References
49
Citations by year
2026: 26 · 2025: 44 · 2024: 42 · 2023: 51 · 2022: 74 · 2021: 62 · 2020: 47 · 2019: 28 · 2018: 7
FWCI
12.90
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Death and Disease (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • National Natural Science Foundation of China (81402148, 81372641, 81672363, 81472244, 81772525)
  • Shanghai Jiao Tong University
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords
tumor-associated macrophages, exosomes, gastric cancer, apolipoprotein E, cell migration, M2 macrophages, tumor microenvironment, intercellular protein transfer, PI3K/Akt signaling, cytoskeletal remodeling, metastasis
MeSH terms
Phosphoinositide-3 Kinase Inhibitors, Aniline Compounds, Animals, Apolipoproteins E, Benzylidene Compounds, Cell Movement, Cytoskeleton, Humans, Lung Neoplasms, Macrophages, Stomach Neoplasms, Signal Transduction, Phosphatidylinositol 3-Kinases, Cell Line, Tumor, Proto-Oncogene Proteins c-akt, Mice, Exosomes

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