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Programming of macrophages by UV-irradiated apoptotic cancer cells inhibits cancer progression and lung metastasis
- Title
- Programming of macrophages by UV-irradiated apoptotic cancer cells inhibits cancer progression and lung metastasis
- Authors
- Kim Y.-B.; Ahn Y.-H.; Jung J.-H.; Lee Y.-J.; Lee J.-H.; Kang J.L.
- Ewha Authors
- 이지희; 이진화; 안영호; 김용배
- SCOPUS Author ID
- 이지희; 이진화; 안영호; 김용배
- Issue Date
- 2019
- Journal Title
- Cellular and Molecular Immunology
- ISSN
- 1672-7681
- Citation
- Cellular and Molecular Immunology vol. 16, no. 11, pp. 851 - 867
- Keywords
- Apoptotic cell clearance; EMT; Exosomal PTEN; Metastasis; PPARγ ligands
- Publisher
- Chinese Soc Immunology
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Apoptotic cell clearance by phagocytes is essential in tissue homeostasis. We demonstrated that conditioned medium (CM) from macrophages exposed to apoptotic cancer cells inhibits the TGFβ1-induced epithelial–mesenchymal transition (EMT), migration, and invasion of cancer cells. Apoptotic 344SQ (ApoSQ) cell-induced PPARγ activity in macrophages increased the levels of PTEN, which was secreted in exosomes. Exosomal PTEN was taken up by recipient lung cancer cells. ApoSQ-exposed CM from PTEN knockdown cells failed to enhance PTEN in 344SQ cells, restore cellular polarity, or exert anti-EMT and anti-invasive effects. The CM that was deficient in PPARγ ligands, including 15-HETE, lipoxin A4, and 15d-PGJ2, could not reverse the suppression of PPARγ activity or the PTEN increase in 344SQ cells and consequently failed to prevent the EMT process. Moreover, a single injection of ApoSQ cells inhibited lung metastasis in syngeneic immunocompetent mice with enhanced PPARγ/PTEN signaling both in tumor-associated macrophages and in tumor cells. PPARγ antagonist GW9662 reversed the signaling by PPARγ/PTEN; the reduction in EMT-activating transcription factors, such as Snai1 and Zeb1; and the antimetastatic effect of the ApoSQ injection. Thus, the injection of apoptotic lung cancer cells may offer a new strategy for the prevention of lung metastasis. © 2019, The Author(s).
- DOI
- 10.1038/s41423-019-0209-1
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
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