Arginase inhibition suppresses lung metastasis in the 4T1 breast cancer model independently of the immunomodulatory and anti-metastatic effects of VEGFR-2 blockade.

ABSTRACT: Tumor angiogenesis promotes tumor growth and metastasis. Anti-angiogenic therapy in combination with chemotherapy is used for the treatment of metastatic cancers, including breast cancer but therapeutic benefits are limited. Mobilization and accumulation of myeloid-derived suppressor cells (MDSC) during tumor progression and therapy have been implicated in metastasis formation and resistance to anti-angiogenic treatments. Here, we used the 4T1 orthotopic syngenic mouse model of mammary adenocarcinoma to investigate the effect of VEGF/VEGFR-2 axis inhibition on lung metastasis, MDSC and regulatory T cells (Tregs). We show that treatment with the anti-VEGFR-2 blocking antibody DC101 inhibits primary tumor growth, angiogenesis and lung metastasis. DC101 treatment had no effect on MDSC mobiliz

SUBMITTER: Secondini C 

PROVIDER: S-EPMC5486183 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature