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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
이지희이진화안영호김용배
SCOPUS Author ID
이지희scopus; 이진화scopus; 안영호scopus
Issue Date
2019
Journal Title
Cellular and Molecular Immunology
ISSN
1672-7681JCR Link
Citation
Cellular and Molecular Immunology vol. 16, no. 11, pp. 851 - 867
Keywords
Apoptotic cell clearanceEMTExosomal PTENMetastasisPPARγ ligands
Publisher
Chinese Soc Immunology
Indexed
SCIE; SCOPUS WOS 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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