Bone metastasis: Histological changes and pathophysiological mechanisms in osteolytic or osteosclerotic localizations. A review

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 spec...

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Bibliographic Details
Published in:Morphologie 2011-06, Vol.95 (309), p.65-75
Main Authors: Chappard, D., Bouvard, B., Baslé, M.-F., Legrand, E., Audran, M.
Format: Article
Language:English
Subjects:
Adenocarcinoma - pathology
Adenocarcinoma - physiopathology
Adenocarcinoma - secondary
Biological and medical sciences
Bone Density Conservation Agents - therapeutic use
Bone malignancy
Bone Marrow - pathology
Bone metastasis
Bone Neoplasms - complications
Bone Neoplasms - pathology
Bone Neoplasms - physiopathology
Bone Neoplasms - secondary
Bone Remodeling - physiology
Breast Neoplasms - pathology
Cancer secondaire des os
Diphosphonates - therapeutic use
Female
Fundamental and applied biological sciences. Psychology
Humans
Intercellular Signaling Peptides and Proteins - physiology
Life Sciences
Male
Models, Biological
Métastase osseuse
Neoplasm Proteins - physiology
Osteolysis
Osteolysis - etiology
Osteolysis - pathology
Osteolysis - physiopathology
Osteolysis - prevention & control
Osteosclerosis
Osteosclerosis - etiology
Osteosclerosis - pathology
Osteosclerosis - physiopathology
Osteosclerosis - prevention & control
Ostéolyse
Ostéosclérose
Pathophysiology
Physiopathologie
Prostatic Neoplasms - pathology
RANK Ligand - physiology
Receptor Activator of Nuclear Factor-kappa B - physiology
Signal Transduction
Tumor Microenvironment
Vertebrates: anatomy and physiology, studies on body, several organs or systems
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Summary: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. Le développement d’une métastase osseuse implique des interactions entre les cellules malignes, le microenvironnement médullaire et les cellules osseuses elles-mêmes. L’analyse histopathologique d’échantillons osseux envahis par une métastase permet d’aborder les mécanismes physiopathologiques de la progression tumorale. La présente revue fait le point des principaux mécanismes moléculaires impliqués dans la localisation et le développement des cellules malignes dans l’os. Les stades de progression sont illustrés dans les métastases ostéolytiques (ou mixtes) et dans les formes ostésclérotiques par des clichés microscopiques en coloration standard et immunohistochimie ainsi que par microtomographie aux rayons X. Dans les deux cas, les cellules tumorales trouvent dans le microenvironnement médullaire un « sol fertile » qui va favoriser leur croissance. Elles utilisent les facteurs de croissance libérés par les cellules osseuses (et servant physiologiquement au couplage ostéoclastes/ostéoblastes) comme promoteur de leur propre expansion. En retour, elles libèrent de nombreuses cytokines qui stimulent localement l’ostéoclastogenèse (PTHrP, IL-1, IL-6…) ou, à l’inverse, d’autres facteurs qui augmentent considérablement l’activité ostéoblastique (ET
ISSN:1286-0115
DOI:10.1016/j.morpho.2011.02.004