Tumor-Host Interactions in Breast Cancer Bone Metastasis

Abstract : The proposal will test the hypothesis that bone represents a unique microenvironment favoring the survival and growth of metastatic breast cancer cells. Further, that cells in breast cancer bone metastases are specialized populations of cancer cells, endowed with properties that promote their growth in bone. The presence of breast cancer cells can disrupt the normal balance of bone turnover and promote osteoclast activity. Understanding the biology of breast cancer bone metastases and the contribution of cancer cell-derived factors, such as platelet derived growth factor (PDGF), will lead to new approaches for control or prevention of this significant clinical problem. Expression analyses will be performed using cDNA arrays, testing samples from breast cancer cell lines growing in different conditions - in vitro and in vivo (direct injection into bone or mammary fatpad, and/or metastases from different organs in mice). The arrays to be used will identify cytokines and receptors, and genes involved in specific pathways (cell cycle regulation, cell death, metastasis and invasion, signal transduction, angiogenesis). One of the factors known to promote bone resorption is PDGF, and the consequences of the release of PDGF by metastatic breast cancer cells will be determined in in vitro experiments with immortalized osteoblasts.