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.