RT Journal Article SR Electronic T1 MMP9 modulates the metastatic cascade and immune landscape for breast cancer anti-metastatic therapy JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e201800226 DO 10.26508/lsa.201800226 VO 2 IS 6 A1 Owyong, Mark A1 Chou, Jonathan A1 van den Bijgaart, Renske JE A1 Kong, Niwen A1 Efe, Gizem A1 Maynard, Carrie A1 Talmi-Frank, Dalit A1 Solomonov, Inna A1 Koopman, Charlotte A1 Hadler-Olsen, Elin A1 Headley, Mark A1 Lin, Charlene A1 Wang, Chih-Yang A1 Sagi, Irit A1 Werb, Zena A1 Plaks, Vicki YR 2019 UL http://www.life-science-alliance.org/content/2/6/e201800226.abstract AB 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, primary tumor burden was unaffected, suggesting that inhibiting active MMP9 is primarily effective during the early metastatic cascade. These findings suggest that the early metastatic circuit can be disrupted by inhibiting active MMP9 and warrant further studies of MMP9-targeted anti-metastatic breast cancer therapy.