Cellular and molecular basis of preferential metastasis of breast cancer to bone.
Bone is one of the most preferential target sites for cancer metastasis. Breast cancer has a predilection for spreading to bone, and bone metastasis is one of the major causes of increased morbidity and eventual mortality in breast cancer patients. None of the currently available therapies is effective for curing bone metastases in these patients. Elucidation of the cellular and molecular mechanism by which breast cancer selectively spreads to bone is essential for the development of mechanism-based effective and specific therapeutic interventions for this deleterious complication in breast cancer. Here, two questions are addressed to study the mechanism of breast cancer metastasis to bone: (1) What makes bone a preferential target site of metastasis? (2) What makes breast cancer able to colonize bone? (3) An animal model in which intracardiac inoculation of breast cancer cells selectively causes osteolytic bone metastases was developed. Experimental results obtained using this unique in-vivo model of bone metastasis are described and discussed.
Yoneda
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Department of Biochemistry, Osaka University Faculty of Dentistry, 1-8 Yamada-oka, Suita, Osaka 565-0891, Japan.
D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism / Q000556:secondary*; D001862:Bone Resorption / Q000503:physiopathology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism; D004164:Diphosphonates / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000503:physiopathology; D009363:Neoplasm Proteins / Q000378:metabolism; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D015820:Cadherins; D004164:Diphosphonates; D039041:Integrin alpha4beta1; D016023:Integrins; D007797:Laminin; D009363:Neoplasm Proteins; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1; D020782:Matrix Metalloproteinases