Mechanisms of Bone Metastasis from Breast Cancer Using a Clinically Relevant Model
Abstract
We have developed and characterised a model of breast cancer metastasis to bone that overcomes the deficiencies of earlier models. It utilises clones of a spontaneous mammary carcinoma that, after orthotopic injection of the tumor cells into the mammary gland, metastasise to bone and cause hypercalcemia. In addition, metastases are detected in some other organs, mainly lungs and liver. Other clones derived from the same primary tumor either do not metastasise, or metastasise only to lungs. In the past year, we have made substantial progress in two areas. One is in a study of the role of a gene, parathyroid hormone related protein (PTHrP), believed to be important in metastasis to bone. We have found that expression of PTHrP is not required for metastasis to bone, but once in the bone environment, high levels of PTHrP enhance tumor growth. This is consistent with a recent clinical study of the link between PTHrP and bone metastasis. Our genome wide screening for genes required for metastasis to bone has revealed several candidates, all but one of which have not been implicated previously in metastasis. They are caveolin- 1, bone morphometric protein-4, osteopontin, protease nexin-l and (33 integrin. Functional studies are underway with these genes.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADA387843
Entities
People
- Robin Anderson
Organizations
- Peter MacCallum Cancer Centre