Tumor metastasis to bone 英文参考文献.docVIP

Available online /content/9/S1/S5 Review Tumor metastasis to bone Mandeep S Virk and Jay R Lieberman The New England Musculoskeletal Institute and Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington Avenue, Farmington, Connecticut 06030, USA Correspondence: Jay R Lieberman, jlieberman@ Published: 29 June 2007 Arthritis Research Therapy 2007, 9(Suppl 1):S5 (doi:10.1186/ar2169) This article is online at /content/9/S1/S5 ? 2007 BioMed Central Ltd Abstract bone from breast cancer can be osteoblastic, osteolytic, or mixed. Irrespective of the mechanisms that are involved in the generation of these radiographic phenotypes, the end result is a change in bone architecture, which predisposes the patient to a variety of skeletal complications [3,5]. Establishment of skeletal metastasis involves bidirectional inter- actions between the tumor cell and the cellular elements in the bone microenvironment. A better understanding of the patho- physiology of bone metastasis will be critical in developing the means to prevent bone metastasis or inhibit its progression. The receptor activator of nuclear factor-κB (RANK)/RANK ligand pathway has emerged as the key pathway regulating osteolysis in skeletal metastasis. A number of candidate factors, including the Wnt (wingless int) proteins, endothelin-1, and bone morphogenetic proteins, have been implicated in the establishment of osteoblastic metastasis. The complex nature of tumor-bone microenvironment interactions and the presence of multiple pathways that lead to bone metastasis suggests that simultaneous targeting of these pathways in the metastatic cascade are required for effective treatment. This review discusses current understanding of the pathophysiologic mechanisms that underlie the establishment of bone metastasis and potential molecular therapeutic strategies for preventi