Targeting Neutrophil Protease-Mediated Degradation of Tsp-1 to Induce Metastatic Dormancy
Abstract
We hypothesize that intervention against inflammation-driven NE/CG- 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 NE/CG-Tsp-1 axis is the dominant pathway in inflammation-mediated metastasis, 2) to determine the molecular mechanisms by which neutrophil CG/NE-Tsp-1 axis promotes metastasis, 3) to show that NE/CG-Tsp-1 axis modulates Tsp-1-mediated metastatic dormancy, 4) to assess whether pharmacological inhibition of CG/NE 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2019
- Accession Number
- AD1095323
Entities
People
- Vivek Mittal
Organizations
- Weill Cornell Medicine