No conflicts of interest were declared.
Epiphyseal growth plate and secondary peripheral chondrosarcoma: the neighbours matter†
Article first published online: 23 NOV 2011
Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Special Issue: The Cell Biology of Disease
Volume 226, Issue 2, pages 219–228, January 2012
How to Cite
de Andrea, C. E. and Hogendoorn, P. C. (2012), Epiphyseal growth plate and secondary peripheral chondrosarcoma: the neighbours matter. J. Pathol., 226: 219–228. doi: 10.1002/path.3003
- Issue published online: 1 DEC 2011
- Article first published online: 23 NOV 2011
- Accepted manuscript online: 28 SEP 2011 04:08AM EST
- Manuscript Accepted: 22 SEP 2011
- Manuscript Revised: 20 SEP 2011
- Manuscript Received: 10 AUG 2011
- growth plate;
- primary cilia;
- bone tumour
Chondrocytes interact with their neighbours through their cartilaginous extracellular matrix (ECM). Chondrocyte–matrix interactions compensate the lack of cell–cell contact and are modulated by proteoglycans and other molecules. The epiphyseal growth plate is a highly organized tissue responsible for long bone elongation. The growth plate is regulated by gradients of morphogens that are established by proteoglycans. Morphogens diffuse across the ECM, creating short- and long-range signalling that lead to the formation of a polarized tissue. Mutations affecting genes that modulate cell–matrix interactions are linked to several human disorders. Homozygous mutations of EXT1/EXT2 result in reduced synthesis and shortened heparan sulphate chains on both cell surface and matrix proteoglycans. This disrupts the diffusion gradients of morphogens and signal transduction in the epiphyseal growth plate, contributing to loss of cell polarity and osteochondroma formation. Osteochondromas are cartilage-capped bony projections arising from the metaphyses of endochondral bones adjacent to the growth plate. The osteochondroma cap is formed by cells with homozygous mutation of EXT1/EXT2 and committed stem cells/wild-type chondrocytes. Osteochondroma serves as a niche (a permissive environment), which facilitates the committed stem cells/wild-type chondrocytes to acquire secondary genetic changes to form a secondary peripheral chondrosarcoma. In such a scenario, the micro-environment is the site of the initiating processes that ultimately lead to cancer. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.