Breast Cancer Stimulation of Osteolysis
Abstract
In the three years of funding, we have completed analysis of two tumors and have found mRNA and protein for GM-C SF, IGF-I and II, PThrP, and TNF-alpha. We have also studied a mouse model for metastatic tumor development and determined that there is variable filming of the appearance of tumor-derived factors during tumor development. We have examined these factors for their effects on apoptosis and found that TNF-alpha, but not GM-CSF, IGF-I or II, or PTilrP stimulate apoptosis of purified mouse osteoclast-like cells. We have also determined that TNF-a, but not GM-C SF, 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. 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 Tl'lF<x had elevated secretion of TRAP. Taken together
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2000
- Accession Number
- ADB264610
Entities
People
- Merry J. Oursler
Organizations
- University of Minnesota Duluth