RT Journal Article
SR Electronic
T1 Programming of macrophages by apoptotic cancer cells inhibits cancer progression through exosomal PTEN and PPARγ ligands
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 217562
DO 10.1101/217562
A1 Yong-Bae Kim
A1 Young-Ho Ahn
A1 Jin-Hwa Lee
A1 Jihee Lee Kang
YR 2017
UL http://biorxiv.org/content/early/2017/11/10/217562.abstract
AB 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 PPARγ 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 PPARγ ligands could not reverse the suppression of PPARγ 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 PPARγ/PTEN signaling both in tumor-associated macrophages and tumor cells. PPARγ antagonist GW9662 reversed PTEN signaling and anti-metastatic effect. Thus, apoptotic cancer cell therapy may offer a new strategy for the prevention of metastasis.