Imagine you’re in an army convoy, carrying vital information and heading along the road towards a bridge across a deep gorge. But the bridge has been blown out by enemy fire. So the engineers are called in. They get to work, clearing the debris and slinging ropes across the gorge to act as a ‘guide track’, eventually building a new structure for you to drive across.
You may wonder what this military imagery is doing on a cancer blog, but it’s actually a good metaphor for what happens when the nerves that supply our limbs and organs get damaged, whether by injury or surgery.
Cut nerves can regrow across short distances – like the damaged bridge being rebuilt across the gorge – but this process only seems to happen after specialist ‘engineer’ cells, called Schwann cells, lay down molecular ‘guide tracks’.
Professor Alison Lloyd and her team at University College London recently uncovered the molecular signals that guide this repair process. And their findings could have implications for our understanding of how some tumours – such as neurofibroma – may spread through the nervous system.
Laying down tracks
The nerves in our peripheral nervous system are pretty good at repairing themselves –this ability can even extend to regrowth of nerves into reattached limbs or fingers – and Schwann cells play a vital role in this process.
Schwann cells usually act as ‘insulation’ around our nerves – like plastic around electrical wires, they form a sheath around nerve fibres and help them to conduct electrical impulses quickly and efficiently. But when a nerve is cut or damaged, they switch into a different role.
First on the scene of nerve damage are fibroblasts – cells that produce the ‘glue’ that holds our cells together. In addition, fibroblasts also produce important ‘signal’ molecules that alert nearby Schwann cells. Like the engineers in our military tale, the Schwann cells clear any debris left from the area, and form ‘guide tracks’ that direct the growth of the repairing nerve – this is known as a ‘nerve bridge’.
In their new paper, published recently in the journal Cell, Professor Lloyd and her team revealed the identity of these signals.
Using an animal model, the researchers found that fibroblasts release a protein called ephrin-B when they gather at a cut nerve. Ephrin is used throughout the body to direct cells to the right location, and keep them there. And faults in this process have been implicated in some types of cancer.
The team found that Schwann cells responded to ephrin produced by nearby fibroblasts, gathering together at the site of a nerve injury and organising into ‘nerve bridges’, enabling the nerve to repair across the gap. Intriguingly, the two types of cells stayed as separate ‘regiments’, rather than mixing and mingling. So it’s clear that ephrin is used by the cells to organise themselves and ‘know their place’.
Importantly, the scientists discovered that switching off ephrin production halted nerve repair. Without the signals, the Schwann cells failed to cluster and organise themselves, or build nerve bridges.
Linking nerve repair to cancer spread
Professor Lloyd’s findings reveal important new insights into how our nerves are repaired, which will be useful for researchers working on techniques such as nerve grafts, to repair nerves damaged by accidents or surgery.
But we also know that some types of cancer can spread along nerve cells. For example, neurofibroma tumours start in the peripheral nervous system, and spread along the nerves. They are commonly treated with surgery, and – in severe cases – patients can require limb amputation.
Professor Lloyd suspects that cancer cells may be using the same tactics that Schwann cells and fibroblasts employ to fix damaged nerves. In a normal repair job, the regrowth signals would be switched off when the nerves have grown across the wound. But in cancer, it may be the case that the signals don’t get switched off.
So cancer cells carry on spreading along the nerves, rather than ever settling down and ‘healing’. Professor Lloyd also suspects that ephrin signalling is involved here too, but more work is needed to prove this idea.
At the moment, this is still at a speculative stage and a lot more research needs to be done. But investigating these ideas could lead to new ways to block cancers from spreading.
Parrinello, S., et al (2010). EphB Signaling Directs Peripheral Nerve Regeneration through Sox2-Dependent Schwann Cell Sorting Cell, 143 (1), 145-155 DOI: 10.1016/j.cell.2010.08.039
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