Fibrin(ogen) -Mediated Extracellular Transport of Breast Cancer Cells by Macrophages: A New Idea Regarding Metastasis
Abstract
We set out to test the hypothesis that fibrin tethers existing between macrophages and breast cancer cells facilitate the extracellular transport of tumor cells by macrophages. We successfully developed a model system to test our hypothesis, and used it to collect preliminary evidence in support of our theory. During the course of our research, we discovered that fibrin-coated droplets of olive oil - like fibrin-coated macrophages - bind avidly to fibrin-coated murine breast tumor cells in viva. Because of its potential for intermediate application to the treatment of breast and other cancers, we exploded our observation to develop a new vehicle by which% to deliver lipophobic anti-cancer agents, e.g., docetaxel, to fibrin-coated tumors. Using the ascites form of the TA3/St murine mammary tumor, we showed that microscopic droplets of olive oil loaded with docetaxel and coated with fibrinogen prolong the survival of tumor-bearing mice by about 4 times with respect to survival conferred by the standard formulation of docetaxel, i.e., Taxotere. (The results of our studies have now been published in Cline Cancer Res, 10:7001-7010, 2004. A copy of that document is included with his report.) The survival benefit conferred by fibrinogen-coated droplets of docetaxel-loaded olive oil appears to be due to the thromiin- dependent retention of the drug-loaded droplets within the tumor microenvironment. With regard to the original hypothesis, we now propose that fibrinogen-coated particulate formulations of anti-cancer agents might be best suited to treating metastatic disease because macrophage-mediated trafficking of fibrinogen-coated, (rug-loaded particles likely mimics macrophage-mediated trafficking of fibrinogen-coated tumor cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2004
- Accession Number
- ADA432439
Entities
People
- Gregory S. Retzinger
Organizations
- University of Cincinnati