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

Mark Owyong, Jonathan Chou, Renske J.E. van den Bijgaart, Niwen Kong, Gizem Efe, Carrie Maynard, Dalit Talmi-Frank, Inna Solomonov, Charlotte Koopman, Elin Hadler-Olsen, Mark Headley, Charlene Lin, Chih Yang Wang, Irit Sagi, Zena Werb, Vicki Plaks

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article numbere201800226
JournalLife Science Alliance
Volume2
Issue number6
DOIs
Publication statusPublished - Jan 1 2019

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ASJC Scopus subject areas

  • Ecology
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Plant Science
  • Health, Toxicology and Mutagenesis

Cite this

Owyong, M., Chou, J., van den Bijgaart, R. J. E., Kong, N., Efe, G., Maynard, C., Talmi-Frank, D., Solomonov, I., Koopman, C., Hadler-Olsen, E., Headley, M., Lin, C., Wang, C. Y., Sagi, I., Werb, Z., & Plaks, V. (2019). MMP9 modulates the metastatic cascade and immune landscape for breast cancer anti-metastatic therapy. Life Science Alliance, 2(6), [e201800226]. https://doi.org/10.26508/lsa.201800226