Molecular signal behind nerve repair may have role in tumour spread

Cancer Research UK

CANCER RESEARCH UK scientists have discovered how tumours may spread throughout the peripheral nervous system – by mimicking signals given out when nerves are repaired, reveals research published in Cell today.

The peripheral nervous system consists of the nerves in the body which link limbs and organs and tissues to the central nervous system – allowing people to move, feel, and breathe. Remarkably, peripheral nerves can regenerate effectively even after a severe injury – and this is important for re-establishing function following, for example, the reattachment of an amputated limb.

When a nerve is cut, the central, conducting part of the nerve – the axons - have to regrow. The direction of growth of the axons is guided by specialised nerve cells called Schwann cells and also fibroblasts.

The scientists at the MRC Laboratory for Molecular Cell Biology based at UCL (University College London) identified in rodents a new cell signal that plays a crucial role in guiding axon regrowth in the repair of severed nerves.

Tumours in the nervous system often develop from Schwann cells that contain DNA faults. They can spread along the nerves in a way that resembles the movement of healthy Schwann cells and fibroblasts as they repair severed nerves. So the newly discovered molecular signals may also be involved in the spread of tumour cells along nerves.

Lead author, Professor Alison Lloyd from UCL, said: “This intriguing research show us that tumours may spread by acting like an unrepaired wound which is constantly trying to heal.

“We think that the molecules we have discovered that are important in the repair of nerves may also be involved in the spread of tumour cells.

“Many other tumour types appear to spread in a similar way, so it will be of great interest to explore the role of these molecules in the spread of tumours in other tissues.”

Once a nerve is damaged, Schwann cells emerge from both ends of the damaged nerve stumps and make contact with fibroblast cells, which gather together at the injury site.

A receptor molecule called EphB2 present on Schwann cells receives ‘signals’ from a protein called ephrin B which is present on fibroblasts. This signal makes *Schwann cells ‘stick’ to each other to organise themselves into rows of cells – in effect ‘guide ropes’ to direct regrowing nerve cell axons across the wound to reconnect and repair the nerve.

Dr Lesley Walker, director of cancer information at Cancer Research UK, said: “This is very exciting research and it’s a great example of how knowledge in other fields of research such as neurobiology can provide vital insights for understanding cancer. Now we have this fundamental piece of information, further research could identify ways to stop tumours spreading.”

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References

EphB signalling directs peripheral nerve regeneration through Sox2-dependent Schwann Cell sorting. Cell. Parrinello et al.

Notes to Editor

*In healthy nerves Schwann cells wrap around the axons of the nerve and have an important role in the fast transmission of nerve signals. Upon injury however, they coordinate nerve cell repair.

Fibroblasts were known to be important in producing chemicals to recruit immune cells to the injury site and helping to create scar tissue once a nerve cell has been repaired. The scientists additionally found that fibroblasts act in a completely different way by directly signalling to the Schwann cells to heal the injury.