Characterization of Clustered CTCs to Eliminate Breast Cancer Metastasis
Abstract
In year 4 of this award we have securely grounded this project in evaluable data that indicate that this work is an important project to understand mechanism(s) for breast cancer metastasis. We have developed a workable model to detect breast cancer metastasis. Using cell sorting, we prepared an enriched population of Td-tomato E0771.LMC cells that have a high rate of luminescence. Our studies show that enriched E0771.LMC cells with a high percentage of Td-tomato expression have a correlated high rate of bioluminescence. Further, we learned that there is no receptor for IL-11 on platelets. CD44 is on platelets and E0771 LMC cells, but CD49b is only on platelets. Additional studies show that mice are made thrombocytopenic (85% reduction in their starting platelet counts) with 10 g injection of a heterologous antibody to CD41 within 24 h. If E0771.LMC cells with a luciferase marker are injected (3 X 105 cells/ml) into these thrombocytopenic mice, there is significantly less tumor seeding and growth in the lungs at 28 days and there are reduced metastatic lesions in the lungs at 22 to 28 days. Although antibody to platelet CD44 or CD49b induce thrombocytopenia in mice, they, along with IL-11 treatment of mice, have no influence on breast cancer metastasis in this animal model. These data indicate that thrombocytopenia alone at the time of tumor cell injection is not sufficient to influences tumor cell seeding and metastasis. Reduction in tumor lung metastasis is not produced by thrombocytopenia alone, but by interference with platelet beta integrin (CD41) not CD44 or CD49b (platelet alpha integrin).
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2020
- Accession Number
- AD1150351
Entities
People
- Alvin H. Schmaier
Organizations
- Case Western Reserve University