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

Authors :
Chih Yang Wang
Charlotte D. Koopman
Jonathan Chou
Niwen Kong
Mark B. Headley
Carrie Maynard
Charlene Lin
Zena Werb
Renske J.E. van den Bijgaart
Dalit Talmi-Frank
Irit Sagi
Vicki Plaks
Mark Owyong
Inna Solomonov
Gizem Efe
Elin Synnøve Hadler-Olsen
Source :
Life science alliance, vol 2, iss 6, Life Science Alliance, 2, Life Science Alliance, Life Science Alliance, 2, 6
Publication Year :
2019
Publisher :
eScholarship, University of California, 2019.

Abstract

Inhibition of active MMP9 early during tumorigenesis suppresses tumor cell migration, invasion, and colony formation and tilts the balance towards anti-tumor immunity by activating CD8+ T cells.<br />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.

Details

ISSN :
25751077
Database :
OpenAIRE
Journal :
Life science alliance, vol 2, iss 6, Life Science Alliance, 2, Life Science Alliance, Life Science Alliance, 2, 6
Accession number :
edsair.doi.dedup.....9f19a56d83f85c84a28ad246454f4f13