Breast cancer-derived factors facilitate osteolytic bone metastasis.
Bone is the most common site of breast cancer metastasis. Skeletal metastases resulting from breast cancer are most often osteolytic, and contribute to the morbidity and mortality associated with this disease. Over the past several years, significant effort has been focused on elucidating the molecular mechanisms that govern this process. To accomplish this task, animal model systems have been generated to study the process of breast cancer metastasis to bone. These include: intraosseous injection that models tumor growth in the bone marrow, cardiac injections that permit cancer cell dissemination to the bone marrow from the bloodstream, and spontaneous bone metastasis originating from the mammary gland. Importantly, these various model systems have been combined with gene expression profiling to compare breast cancer populations with distinct bone metastatic potentials in the hopes of finding the genes that facilitate this process. The result has been the accumulation of an impressive body of evidence detailing a complex web of interactions between breast cancer cells, the mineralized bone matrix and host cells resident in bone; such as osteoblasts, osteoclasts and bone marrow endothelium. In this review we will address new developments that underscore the importance of secreted proteins and cell surface receptors expressed on breast cancer cells that play key roles in promoting bone resorption and tumor growth. Recent results from both basic and clinical research reveal that similar metastatic functions, such as adhesion and invasion, are conserved across a variety of bone metastatic breast cancer cells and different sets of genes can fulfill these requirements.
Rose
April A N
AA
Department of Medicine, McGill University, 740 Dr. Penfield Avenue, Room 2201, Montreal, Quebec, Canada, H3A 1A4.
Siegel
Peter M
PM
D000222:Adaptation, Physiological; D000818:Animals; D001846:Bone Development / Q000502:physiology; D001859:Bone Neoplasms / Q000503:physiopathology / Q000556:secondary*; D001862:Bone Resorption / Q000209:etiology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D002450:Cell Communication / Q000502:physiology; D045744:Cell Line, Tumor / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D009362:Neoplasm Metastasis / Q000473:pathology / Q000503:physiopathology; D009363:Neoplasm Proteins / Q000502:physiology*; D010006:Osteoblasts / Q000502:physiology; D010010:Osteoclasts / Q000502:physiology; D010014:Osteolysis / Q000209:etiology
D008565:Membrane Proteins; D009363:Neoplasm Proteins