Glufosinate constrains synchronous and metachronous metastasis by promoting anti-tumor macrophages

ABSTRACT: Glutamine synthetase (GS) generates glutamine from glutamate and controls the release of inflammatory mediators. In macrophages GS activity, driven by IL10, associates to the acquisition of M2-like functions. Conditional deletion of GS in macrophages inhibits metastasis by boosting the formation of anti-tumor, M1-like, tumor-associated macrophages (TAMs). From this basis, we evaluated the pharmacological potential of GS inhibitors in targeting metastasis, identifying glufosinate as a specific human GS inhibitor. Glufosinate was tested in both cultured macrophages and on mice bearing metastatic lung, skin and breast cancer. We found that glufosinate rewires macrophages towards an M1-like phenotype both at the primary tumor and metastatic site, countering immunosuppression and promoting vess

SUBMITTER: Alessio Menga 

PROVIDER: S-SCDT-EMM-2019-11210 | biostudies-other |

REPOSITORIES: biostudies-other