Breast Tumor-Generated Type 1 Collagen Breakdown Fragments Act as Matrikines to Drive Osteolysis
Annual rept. 1 Sep 2008-31 Aug 2009
HENRY FORD HEALTH SYSTEM DETROIT MI
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The major site of metastasis of breast cancer cells is bone. Bone metastases occur in 80 of patients with advanced disease and causes significant morbidity. The mechanisms of osteolysis and targeting of bone by the breast cancer cells are still unknown. The osteolysis that occurs in patients is mediated by factors that come from the tumor cells. The tumor cells provide a microenvironment to the osteoblasts and osteoclasts. Bone remodeling requires the degradation and turnover of type I collagen. Type I collagen is a triple helical fibrillar collagen that can be cleaved by cathepsin K found only in osteoclasts. Recently, studies of breakdown fragments of extracellular matrix ECM proteins have shown novel biological activity of the fragments. We believe that these fragments may be chemotactic to breast tumor cells. Once the breast tumor cells metastasize to the bone, the tumor cells secrete factors that stimulate the increase in osteolysis of bone. This leads to increase of type I collagen fragments that signal back to the tumor cells, osteoblasts and osteoclasts perpetuating this cascade. This study proposes to map the active sequences in the type I collagen breakdown fragments that can contribute to breast tumor metastasis to bone. The understanding of this pathway can lead to development of biomarkers assays to detect early bone metastases, monitor treatments in targeting bone metastases and staging of metastatic bone tumors. Prevention, early detection and treatment of bone metastasis breast tumors to bone would benefit the survival and quality of life of breast cancer patients.
- Anatomy and Physiology
- Medicine and Medical Research