Role of Macrophage-Induced Inflammation in Mesothelioma
Abstract
Macrophages are the first inflammatory cells to respond to asbestos fibers and we have shown that they are the predominant inflammatory cell in the asbestos-induced tumor, mesothelioma. We are beginning to unravel the role of the macrophage in this intractable tumor, using in vitro models of macrophages grown with mesothelioma cells, ex vivo models of human mesothelioma maintained as tumor fragment spheroids, and in 2 in vivo models of immunocompetent murine mesothelioma. In this first year, we have confirmed by immunohistochemistry and by flow cytometry of fresh tumor that macrophages are the main inflammatory cell in mesothelioma. We have shown that we can polarize macrophages to either an M1 (anti-tumor) or M2 (pro-tumor) phenotype and that M1-polarized macrophages (derived from a variety of sources including human mesothelioma) increase mesothelioma cell apoptosis and chemosensitivity. In our first study using an orthotopic murine mesothelioma model, the depletion of macrophages increased the mesothelioma response to chemotherapy. We aim to understand the role of the macrophage and how polarization or depletion of macrophages within the tumor can sensitize the mesothelioma cell to treatment.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2010
- Accession Number
- ADA540724
Entities
People
- V. C. Broaddus
Organizations
- University of California, San Francisco