title: Bone metastasis: histological changes and pathophysiological mechanisms in osteolytic or osteosclerotic localizations. A review.
abstract: The development of a bone metastasis involves interactions between the tumor cells, the bone marrow microenvironment and the bone cells themselves. A better understanding of the pathophysiological changes occurring in bone metastasis can be obtained from histopathological examination of invaded specimens. This review focuses on the main molecular mechanisms implied in the localization and growth of malignant cells in the bone marrow. The corresponding histologic developmental stages are illustrated both in osteolytic (or mixed metastasis) or in the osteosclerotic forms by histological analysis, immunohistochemistry and microcomputed tomographic analysis of bone samples. In both cases, the malignant cells find a "fertile soil" in the bone marrow microenvironment. They use the growth factors released by bone cells for the coupling between osteoclasts/osteoblasts to promote their own development. In turn, they elaborate a variety of cytokines that can promote osteoclastogenesis (PTHrP, IL-1, IL-6…) or on the contrary, other growth factors that can boost the osteoblastic activity (ET1, IGFs). A "vicious circle" occurs between the malignant cells and the bone cells leading to the radiological expression of the metastasis.
authors.affiliation: U922-LHEA, Inserm, IRIS-IBS institut de biologie en santé, CHU d'Angers, 49933 Angers cedex, France. daniel.chappard@univ-angers.fr
authors.forename: D
authors.initials: D
authors.lastname: Chappard
authors.forename: B
authors.initials: B
authors.lastname: Bouvard
authors.forename: M-F
authors.initials: MF
authors.lastname: Baslé
authors.forename: E
authors.initials: E
authors.lastname: Legrand
authors.forename: M
authors.initials: M
authors.lastname: Audran
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000503:physiopathology / Q000556:secondary; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D001853:Bone Marrow / Q000473:pathology; D001859:Bone Neoplasms / Q000150:complications / Q000473:pathology / Q000503:physiopathology / Q000556:secondary*; D016723:Bone Remodeling / Q000502:physiology; D001943:Breast Neoplasms / Q000473:pathology; D004164:Diphosphonates / Q000627:therapeutic use; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D008297:Male; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000502:physiology; D010014:Osteolysis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D010026:Osteosclerosis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D011471:Prostatic Neoplasms / Q000473:pathology; D053245:RANK Ligand / Q000502:physiology; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000502:physiology; D015398:Signal Transduction; D059016:Tumor Microenvironment
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human