MRC National Institute for Medical Research, London
Science for Health
Tumour angiogenesis is reduced in a mouse model of Down Syndrome
10 June 2010
Down Syndrome is a human disorder caused by having an extra copy of chromosome 21. The presence of the third copy leads to a complex syndrome characterised by learning difficulties, heart defects, early onset Alzheimer’s disease and increased rates of leukaemia. However not all effects of Down Syndrome are negative; notably, people with Down Syndrome have lower rates of solid tumours.
In work led by Professor Kairbaan Hodivala-Dilke (Queen Mary University of London) using a mouse model of Down Syndrome created by Victor Tybulewicz (pictured), in NIMR's Division of Immune Cell Biology, and Elizabeth Fisher (UCL Institute of Neurology), this reduced rate of solid tumours is shown to be caused by less growth of blood vessels into the tumour.
The Tc1 mouse strain, developed jointly by Victor Tybulewicz and Elizabeth Fisher, is a transchromosomic mouse strain carrying a freely segregating human chromosome 21, which recapitulates many of the phenotypes of human Down Syndrome, including defects in brain development, heart development, and behaviour. Professor Hodivala-Dilke’s team used the Tc1 mice to investigate the reasons behind the reduced rates of solid tumours in Down Syndrome people. In line with expectations from human Down Syndrome, they showed that tumours grew more slowly in the Tc1 mice, but, unexpectedly, they found this was due to reduced growth of blood vessels into the tumours, a process termed angiogenesis. Solid tumours require a good blood supply in order to grow and survive and hence reduced angiogenesis leads to slower tumour growth. Professor Hodivala-Dilke’s group went to identify four genes on human chromosome 21 which, when present in three copies, result in decreased angiogenesis.
This work has identified an underlying cause for the reduction in solid tumours seen in Down Syndrome. In addition it has identified a number of novel proteins involved in the control of tumour angiogenesis. These are promising targets for new anti-tumour therapies. This work has shown how studies of Down Syndrome can have an impact on other areas of medical research, such as cancer.
Victor Tybulewicz
Blood vessels in tumours
Click image to view at full-size
Cross-section of tumours grown in wild-type or Tc1 mice shows that the density of blood vessels (red staining for endomucin) is lower in the Tc1 model of Down Syndrome (image courtesy of Professor Hodivala-Dilke)
Original article
The research findings are published in full in:
Tumour angiogenesis is reduced in the Tc1 mouse model of Down Syndrome (2010)
Louise E. Reynolds, Alan R. Watson, Marianne Baker, Tania A. Jones, Gabriela D’Amico, Stephen D. Robinson, Carine Joffre, Sarah Garrido-Urbani, Juan Carlos Rodriguez-Manzaneque, Estefanía Martino-Echarri, Michel Aurrand-Lions, Denise Sheer, Franca Dagna-Bricarelli, Dean Nizetic, Christopher J. McCabe, Andrew S. Turnell, Stephanie Kermorgant, Beat A. Imhof, Ralf Adams, Elizabeth M.C. Fisher, Victor L. J. Tybulewicz, Ian R. Hart and Kairbaan M. Hodivala-Dilke
Nature 465:813–817. Publisher abstract
See also
External links
News categories
© MRC National Institute for Medical Research
The Ridgeway, Mill Hill, London NW7 1AA
Top of page