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MMP9 modulates the metastatic cascade and immune landscape for breast cancer anti-metastatic therapy
- 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.
- Subjects :
- 0301 basic medicine
Lung Neoplasms
Carcinogenesis
Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2]
Health, Toxicology and Mutagenesis
Inbred Strains
Plant Science
MMP9
CD8-Positive T-Lymphocytes
medicine.disease_cause
Metastasis
Mice
0302 clinical medicine
Circulating tumor cell
Neoplasm Metastasis
Lung
Research Articles
Cancer
Tumor
Ecology
Primary tumor
3. Good health
Matrix Metalloproteinase 9
030220 oncology & carcinogenesis
Female
Stem Cell Research - Nonembryonic - Non-Human
Research Article
Biotechnology
Mice, Inbred Strains
Breast Neoplasms
Matrix Metalloproteinase Inhibitors
Biochemistry, Genetics and Molecular Biology (miscellaneous)
Antibodies
Cell Line
03 medical and health sciences
Experimental
Breast cancer
Immune system
Cell Line, Tumor
Breast Cancer
medicine
Animals
Humans
VDP::Medisinske Fag: 700
Neoplasm Invasiveness
business.industry
Prevention
Mammary Neoplasms
Mammary Neoplasms, Experimental
medicine.disease
Stem Cell Research
VDP::Medical disciplines: 700
body regions
030104 developmental biology
HEK293 Cells
Cancer research
business
Subjects
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