Role of the Macrophage Growth Factor, Colony Stimulating Factor-1, in the Etiopathogenesis of Breast Cancer
Abstract
A strong association exists between the over-expression in tumor cells of the mononuclear phagocytic growth factor, colony stimulating factor-1 (CSF-1) and its receptor, the c-fms proto-oncogene product, and the progression of human breast cancer. There is also a strong association between the number of tumor associated macrophages (TAMs) and poor prognosis. Since CSF-1 is the major growth factor regulating cells of the mononuclear phagocytic lineage, we hypothesized that CSF-1 regulates the recruitment and function of these TAMS to the tumors. We tested this hypothesis by crossing mice that had increased susceptibility to mammary gland cancers with mice carrying a null mutation in the CSF-1 gene (Csfm to the op). In the CSF-1 deficient mice, the incidence of tumorigenesis was similar to wild type mice. However, there was a dramatic reduction in the progression of these tumors to the metastatic state in CSF-l deficient mice. In wild-type mice, this transition was correlated with a dramatic macrophage recruitment to sites of invasion of the tumor through the basement membrane. In contrast, in the CSF-1 deficient mice, the tumors were severely depleted in macrophages and they had not progressed to an invasive state. These results strongly support our hypothesis that CSF-1-regulated TAMs play an important role in breast cancer progression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1999
- Accession Number
- ADB258834
Entities
People
- Jeffrey Pollard
Organizations
- Albert Einstein College of Medicine