TY - JOUR T1 - MMP9 modulates the metastatic cascade and immune landscape for breast cancer anti-metastatic therapy JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.201800226 VL - 2 IS - 6 SP - e201800226 AU - Mark Owyong AU - Jonathan Chou AU - Renske JE van den Bijgaart AU - Niwen Kong AU - Gizem Efe AU - Carrie Maynard AU - Dalit Talmi-Frank AU - Inna Solomonov AU - Charlotte Koopman AU - Elin Hadler-Olsen AU - Mark Headley AU - Charlene Lin AU - Chih-Yang Wang AU - Irit Sagi AU - Zena Werb AU - Vicki Plaks Y1 - 2019/12/01 UR - https://www.life-science-alliance.org/content/2/6/e201800226.abstract N2 - 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. ER -