Role of Autocrine Motility Factor in Osteolytic Metastsis
Abstract
Autocrine motility factor (AMF) is expressed by human breast cancer cells, such as MCF7 where its expression is stimulated by heregulin. Tumor cells constitutively secreting mouse AMF caused periosteal new bone formation in two different models of metastasis-an osteoblastic response similar to what is found with about 15% of breast cancers metastatic to bone. Whenever serum AMF concentrations were significantly increased, the animals displayed tumor-associated weight loss (cachexia), a major cause of morbidity and mortality in advanced disease. The effects of AMF on bone were independent of PTHrP, which plays a central role in ostolytic bone metastases. We also have determined the clearance rate of AMF from the mouse circulation. The species-specific effects of AMF remain little understood; so we undertook to clarify the stucture: function relationships involved. We cloned, sequenced and expressed rabbit AMF, for which the x-ray crystallographic data were already partially solved. These results have been published. We also developed a recombinant protein expression system for the mouse and human factors, which we now prepare in 100mg batches. The human factor has been crystallized and the x-ray structure solved to 1.8A.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2001
- Accession Number
- ADA395620
Entities
People
- John M. Chirgwin
Organizations
- University of Texas Health Science Center at San Antonio