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

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23 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
文章編號e201800226
期刊Life Science Alliance
2
發行號6
DOIs
出版狀態已發佈 - 一月 1 2019

ASJC Scopus subject areas

  • 生態學
  • 生物化學、遺傳與分子生物學(雜項)
  • 植物科學
  • 健康、毒理學和誘變

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