title: OPG-Fc inhibits ovariectomy-induced growth of disseminated breast cancer cells in bone.
abstract: Dormant disseminated tumour cells can be detected in the bone marrow of breast cancer patients several years after resection of the primary tumour. The majority of these patients will remain asymptomatic, however, ∼ 15% will go on to develop overt bone metastases and this condition is currently incurable. The reason why these dormant cells are stimulated to proliferate and form bone tumours in some patients and not others remains to be elucidated. We have recently shown that in an in vivo model, increasing bone turnover by ovariectomy stimulated proliferation of disseminated tumour cells, resulting in formation of bone metastasis. We now show for the first time that osteoclast mediated mechanisms induce growth of tumours from dormant MDA-MB-231 cells disseminated in the bone. We also show that disruption of RANK-RANKL interactions following administration of OPG-Fc inhibits growth of these dormant tumour cells in vivo. Our data support early intervention with anti-resorptive therapy in a low-oestrogen environment to prevent development of bone metastases.
authors.affiliation: Department of Oncology, Academic Unit of Clinical Oncology, University of Sheffield, S10 2RX, United Kingdom.
authors.forename: Penelope D
authors.initials: PD
authors.lastname: Ottewell
authors.affiliation: Academic Unit of Bone Biology, Department of Human Metabolism, University of Sheffield, S10 2RX, United Kingdom.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Oncology, Academic Unit of Clinical Oncology, University of Sheffield, S10 2RX, United Kingdom.
authors.forename: Hannah K
authors.initials: HK
authors.lastname: Brown
authors.affiliation: Academic Unit of Bone Biology, Department of Human Metabolism, University of Sheffield, S10 2RX, United Kingdom.
authors.forename: C Anne
authors.initials: CA
authors.lastname: Fowles
authors.affiliation: Musculoskeletal Medicine Division, Garvan Institute of Medical Research, Sidney, New South Wales, Australia.
authors.forename: Peter I
authors.initials: PI
authors.lastname: Croucher
authors.affiliation: Academic Unit of Bone Biology, Department of Human Metabolism, University of Sheffield, S10 2RX, United Kingdom.
authors.forename: Colby L
authors.initials: CL
authors.lastname: Eaton
authors.affiliation: Department of Oncology, Academic Unit of Clinical Oncology, University of Sheffield, S10 2RX, United Kingdom.
authors.forename: Ingunn
authors.initials: I
authors.lastname: Holen
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D001862:Bone Resorption / Q000188:drug therapy / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage / Q000276:immunology; D051379:Mice; D010010:Osteoclasts; D053244:Osteoprotegerin / Q000008:administration & dosage* / Q000276:immunology; D010052:Ovariectomy / Q000009:adverse effects*; D053245:RANK Ligand / Q000378:metabolism
chemical_list: D007141:Immunoglobulin Fc Fragments; D053244:Osteoprotegerin; D053245:RANK Ligand
keywords: OPG; bone; breast cancer; metastasis