Breast Cancer Stimulation of Osteolysis

摘要

In this second year of funding, we have completed analysis of two tumors and have found mRNA and protein for GM-CSF, IGF-I and II, PTHrP, and TNF- alpha. We have also determined that TNF-alpha, but not GM-CSF, IGF-I or II, or PTHrP act as survival agents for osteoclast-like cells. When osteoclast-like cells differentiate in the presence of TNF-alpha, withdrawal of TNF-alpha once the mature cells are purified induces apoptosis while continued treatment with TNF-alpha represses apoptosis. We have also examined the activity of cells that are differentiated in the presence of PTHrP and TNF-alpha for resorption activity and lysosomal enzyme secretion. We have found that both treatments, either alone or in combination, result in more active osteoclast-like cells. All treatments resulted in increased resorption and secretion of cathepsin B, but only the cells that differentiated in the presence of TNF-alpha had elevated secretion of TRAP. We are continuing to examine the ramifications of these effects on activity and survival.