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bioRxiv · 10.1101/217562

Programming of macrophages by apoptotic cancer cells inhibits cancer progression through exosomal PTEN and PPARγ ligands

Kim, Y.-B.·Ahn, Y.-H.·Lee, J.-H.·Kang, J. L.
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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 epithelial-mesenchymal transition (EMT), migration, and invasion of cancer cells with the acquisition of cancer-stem-like traits. Apoptotic 344SQ (ApoSQ) cell-induced PPAR{gamma} activity in macrophages caused increased PTEN levels, secreted in exosomes. ApoSQ-exposed CM from PTEN knockdown cells failed to enhance PTEN in recipient 344SQ cells, restore cellular polarity, and exert anti-EMT and anti-invasive effects. The CM which deficient of PPAR{gamma} ligands could not reverse the suppression of PPAR{gamma} activity and PTEN and consequently failed to the prevent EMT process. Moreover, single injection of ApoSQ cells inhibited lung metastasis in syngeneic mice with enhanced PPAR{gamma}/PTEN signaling both in tumor-associated macrophages and tumor cells. PPAR{gamma} antagonist GW9662 reversed PTEN signaling and anti-metastatic effect. Thus, apoptotic cancer cell therapy may offer a new strategy for the prevention of metastasis.

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Kim, Y.-B., Ahn, Y.-H., Lee, J.-H., Kang, J. L.. 2017-11-10. Programming of macrophages by apoptotic cancer cells inhibits cancer progression through exosomal PTEN and PPARγ ligands. https://doi.org/10.1101/217562

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