MMP9 modulates the metastatic cascade and immune landscape for breast cancer anti-metastatic therapy.

ABSTRACT: Metastasis, the main cause of cancer-related death, has traditionally been viewed as a late-occurring process during cancer progression. Using the MMTV-PyMT luminal B breast cancer model, we demonstrate that the lung metastatic niche is established early during tumorigenesis. We found that matrix metalloproteinase 9 (MMP9) is an important component of the metastatic niche early in tumorigenesis and promotes circulating tumor cells to colonize the lungs. Blocking active MMP9, using a monoclonal antibody specific to the active form of gelatinases, inhibited endogenous and experimental lung metastases in the MMTV-PyMT model. Mechanistically, inhibiting MMP9 attenuated migration, invasion, and colony formation and promoted CD8⁺ T cell infiltration and activation. Interestingly, prim

SUBMITTER: Owyong M 

PROVIDER: S-EPMC6856766 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature