Osteoblasts suppress high bone turnover caused by osteolytic breast cancer in-vitro.
The skeleton is the most common site of breast cancer metastasis, which can occur in up to 85% of patients during their lifetime. The morbidity associated with bone metastases in patients with breast cancer includes pathological fractures, bone pain, hypercalcaemia, and spinal cord compression. When breast cancer metastasizes to bone, the balance of bone resorption (mediated by osteoclasts) and bone formation (mediated by osteoblasts) favors bone resorption, which leads to net bone destruction (i.e., osteolysis). Anti-resorptive agents such as bisphosphonates are commonly used to treat bone resorption in osteoporosis or osteolytic cancer patients. However, bisphosphonates by themselves are unable to rebuild lost bone tissue, and can cause severe side effects. In this study, we developed a bovine bone explant culture system and have observed that murine osteoblasts can modulate the activity of osteotropic human breast cancer cells on this substrate. Using markers of bone metabolism, we observe diminished bone turnover in organ culture following the addition of exogenous osteoblasts. The data presented in this study supports further investigation into the use of cytotherapies to limit breast cancer mediated osteolysis.
Department of Oncology, Faculty of Medicine, University of Calgary, Canada. rkrawetz@ucalgary.ca
Roman
R
Krawetz
Yiru Elizabeth
YE
Wu
Derrick E
DE
Rancourt
John
J
Matyas
D000135:Acid Phosphatase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism / Q000556:secondary* / Q000628:therapy*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002417:Cattle; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D006801:Humans; D051379:Mice; D009924:Organ Culture Techniques; D010006:Osteoblasts / Q000378:metabolism / Q000637:transplantation*; D010014:Osteolysis / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*
D000469:Alkaline Phosphatase; D000135:Acid Phosphatase