Targeting Neutrophil Protease-Mediated Degradation of Tsp-1 to Induce Metastatic Dormancy
Technical Report,30 Sep 2018,29 Sep 2019
Joan and Sanford I. Weill Medical College of Cornell University New York United States
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We hypothesize that intervention against inflammation-driven NECG- Tsp-1 axis can be developed into an anti-metastatic therapy in breast cancer. Using a combination of genetic and pharmacological approaches, we propose to achieve the following objectives 1 to establish that the neutrophil NECG-Tsp-1 axis is the dominant pathway in inflammation-mediated metastasis, 2 to determine the molecular mechanisms by which neutrophil CGNE-Tsp-1 axis promotes metastasis, 3 to show that NECG-Tsp-1 axis modulates Tsp-1-mediated metastatic dormancy, 4 to assess whether pharmacological inhibition of CGNE with Sivelestat can be used to inhibit metastasis, and 5 to determine if induction of Tsp-1 expression in the lung microenvironment with a novel DWLPK peptide constitutes an anti-metastatic approach. This project addresses BCRP overarching challenges of revolutionizing treatment regimens by replacing interventions that have life-threatening toxicities with ones that are safe and effective and for advancing the field towards the elimination of mortality associated with metastasis in high-risk breast cancer patients. It also addresses metastatic dormancy, and progression of breast cancer to life threatening metastasis. In summary, we anticipate that the proposed studies will lead to exciting and novel findings that have the potential to impact inflammation-mediated metastasis in breast cancer.
- Medicine and Medical Research