Programming of macrophages by UV-irradiated apoptotic cancer cells inhibits cancer progression and lung metastasis

Yong Bae Kim, Young Ho Ahn, Ji Hae Jung, Ye Ji Lee, Jin Hwa Lee, Jihee Lee Kang

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


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.

Original languageEnglish
Pages (from-to)851-867
Number of pages17
JournalCellular and Molecular Immunology
Issue number11
StatePublished - 1 Nov 2019

Bibliographical note

Publisher Copyright:
© 2019, The Author(s).


  • Apoptotic cell clearance
  • EMT
  • Exosomal PTEN
  • Metastasis
  • PPARγ ligands


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