Bone Factors Regulating the Osteotropism of Metastatic Breast Cancer
Abstract
The specificity with which breast cancer metastasizes to the human skeleton is currently unexplained. In this project we have attempted to identify the critical molecular interactions and cellular processes responsible for this osteotropism (homing and metastatic growth in bone) of breast cancer. The central hypothesis is that malignant breast adenocarcinoma cells subvert the cooperative paracrine interactions between normal bone cells, endothelial cells, and the extracellular matrix in order to establish metastatic foci. Our data combined with published reports show that invasive breast adenocarcinoma cells mimic certain hallmarks of the osteoblast phenotype, possibly explaining the facile growth and survival of these tumor cells in bone. Analysis of model human tumor lines, and derivative sublines recovered from bone metastases in nude mice, reveals a correlation between the degree of malignancy and the inappropriate expression of the "bone specific" transcription factor CBFA1. The osteoblast mimicry by the tumor cells may be explained by CBFA1 expression; normal breast tissue does not express CBFA1. Osteoblast factors also have a paracrine effect on altering the phenotype of breast adenocarcinoma cells in the bone microenvironment.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1999
- Accession Number
- ADB262544
Entities
People
- Peter V. Hauschka