Mechanisms of Bone Metastasis from Breast Cancer Using a Clinically Relevant Model.

摘要

Bone metastases develop in 70% of breast cancer patients who are left untreated or for whom treatment fails. Once the tumor has metastasised, the disease is hard to control and treatment options are limited. A lack of knowledge of the metastasis process and the genes that control it precludes the use of rational drug design. Breast cancer metastasis to bone is poorly understood largely due to a dearth of model systems available to study this process. We have developed a murine model of breast cancer that actively mimics the human disease. After implantation of tumor cells into the mammary gland, a primary tumour develops and subsequently metastasises to the lymph nodes, lung and bone. The resulting bone lysis, paralysis, hypercalcaemia and elevated plasma parathyroid hormone-related protein (PTHrP) are all hallmarks of the human disease. We have used the 3 years of DOD funding to develop and characterize the model and to seek the genes that regulate metastasis to bone. By differential gene expression analysis using two clones that are both metastatic but differ in their ability to metastasise to bone, we have identified candidate genes for bone tumor homing and growth. We have also determined the expression patterns and function of genes already proposed by others to play a role in breast cancer metastasis.