PT  - JOURNAL ARTICLE
AU  - Owyong, Mark
AU  - Chou, Jonathan
AU  - van den Bijgaart, Renske JE
AU  - Kong, Niwen
AU  - Efe, Gizem
AU  - Maynard, Carrie
AU  - Talmi-Frank, Dalit
AU  - Solomonov, Inna
AU  - Koopman, Charlotte
AU  - Hadler-Olsen, Elin
AU  - Headley, Mark
AU  - Lin, Charlene
AU  - Wang, Chih-Yang
AU  - Sagi, Irit
AU  - Werb, Zena
AU  - Plaks, Vicki
TI  - MMP9 modulates the metastatic cascade and immune landscape for breast cancer anti-metastatic therapy
AID  - 10.26508/lsa.201800226
DP  - 2019 Dec 01
TA  - Life Science Alliance
PG  - e201800226
VI  - 2
IP  - 6
4099  - http://www.life-science-alliance.org/content/2/6/e201800226.short
4100  - http://www.life-science-alliance.org/content/2/6/e201800226.full
SO  - Life Sci. Alliance2019 Dec 01; 2
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.