Functional Mechanisms of the Macrophage Growth Factor (CSF-1) and Tumor-Associated Macrophages in Breast Tumor Malignancy
Abstract
The aim of this proposal is to determine the causal role for the mononuclear phagocytic growth factor, CSF-1, overexpressed in human breast cancer, as well as for tumor-associated macrophages in tumor progression. Our recent studies indicate that CSF-1 and CSF-IR play important roles in mammary gland development because CSF-l nullizigous mice (Csfm sup op/Csfm sup op) display ay a failure of branching morphogenesis associated with an almost complete absence of macrophages in Csfm sup op/Csfm sup op mice at mid pregnancy. We tested the hypothesis that the potentiation of ductal cell growth by CSF-I and/or CSF-l recruited macrophages may be similar in both normal and malignant processes by analyzing in vivo the development of mammary gland in the presence (+/Csfm sup op mice) or absence (Csfm op/Csfm op mice) of CSF- I. One of the tumor Csfm sup op/Csfm sup op mammary mouse model in the transgenic MMTV-PyV middle T background showed that in absence of CSF- 1, the tumor progression is delayed and correlated to the lack of macrophage, which are abundant around the carcinoma cells in +/Csfm sup op mice; In parallel, mammary gland postnatal development study demonstrates that CSF- 1 is required for epithelial ductal outgrowth acting through the CSF-1R expressed on epithelial cells and macrophages in order to recruit them around the terminal end buds. These studies, together with ongoing analyses of mamma tumor- susceptible csfm sup op/csfm op mice. will offer insight into the autocrine role of tumor-secreted CSF-I and its paracrine effect on macrophages, emphasizing the importance of stromal/epithelial cell interactions in normal and malignant mammary gland development.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 1999
- Accession Number
- ADB257323
Entities
People
- Valerie B. Gouon
Organizations
- Albert Einstein College of Medicine