Key Points
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Benign cartilage lesions (enchondromas and osteochondromas) can result from the deregulation of the hedgehog signalling pathway, which is involved in normal bone development.
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Malignant chondrosarcomas can derive from benign cartilage lesions, with enchondromas developing into central chondrosarcomas and osteochondromas developing into peripheral chondrosarcomas.
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Peripheral chondrosarcomas have different molecular abnormalities from central chondrosarcomas.
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The progression from benign to malignant cartilage tumours is not driven by hedgehog signalling, but blocking this pathway may be a potential therapeutic target by inducing tumour cartilage cell differentiation.
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Genetically modified mice show that p53 and insulin-like growth factor are deregulated when enchondromas progress to central chondrosarcomas.
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Cytogenetic studies show that cyclin-dependent kinase 4, hypoxia-inducible factor, matrix metalloproteinases, SRC and AKT are activated in central chondrosarcomas, suggesting potential new therapeutic approaches.
Abstract
As a group, cartilage tumours are the most common primary bone lesions. They range from benign lesions, such as enchondromas and osteochondromas, to malignant chondrosarcoma. The benign lesions result from the deregulation of the hedgehog signalling pathway, which is involved in normal bone development. These lesions can be the precursors of malignant chondrosarcomas, which are notoriously resistant to conventional chemotherapy and radiotherapy. Cytogenetic studies and mouse models are beginning to identify genes and signalling pathways that have roles in tumour progression, such as hedgehog, p53, insulin-like growth factor, cyclin-dependent kinase 4, hypoxia-inducible factor, matrix metalloproteinases, SRC and AKT, suggesting potential new therapeutic approaches.
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Acknowledgements
The authors would like to thank Y. Schrage and L. Hameetman for their help with the tables. J.V.M.G.B was financially supported by The Netherlands Organization for Scientific Research (917-76-315).
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Supplementary information
Supplementary information S1
Mouse models to study the formation of cartilaginous tumours with respect to EXT and growth plate signalling (PDF 185 kb)
Supplementary information S2
Model organisms to study the formation of cartilaginous tumours with respect to EXT and growth plate signalling (PDF 188 kb)
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Glossary
- Long bone
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A bone that is longer than it is wide; for example, the femur in the thigh and the humerus in the upper arm.
- Osteoblast
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A cell responsible for bone formation. It expresses bone sialoprotein and osteocalcin and produces osteoid, which is composed mainly of Type I collagen.
- Growth plate
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A specialized region of cartilage, located near the ends of bone, which is responsible for the longitudinal growth of long bones.
- Epiphysis
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The rounded end of a long bone, located closest to the adjacent joint.
- Metaphysis
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The wider portion of a long bone adjacent to the growth plate, but closer to the middle of the bone.
- Muco-myxoid matrix
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Increase of mucopolysaccharides in the extracellular matrix, resulting in pale-to-lightly basophilic staining using haematoxylin and eosin.
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Bovée, J., Hogendoorn, P., Wunder, J. et al. Cartilage tumours and bone development: molecular pathology and possible therapeutic targets. Nat Rev Cancer 10, 481–488 (2010). https://doi.org/10.1038/nrc2869
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DOI: https://doi.org/10.1038/nrc2869
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