Blood vessels (blue) act as 'tracks' for Schwann cells (green) and nerve cells (red) to grow along. Image courtesy of Alison Lloyd.
Thanks to the dexterity of surgeons it’s now possible to reattach severed fingers, toes and even limbs that have been accidentally lost. What’s even more impressive is the capacity of nerves to grow back again, restoring at least some sensation and movement to the damaged digits in many cases.
Nerve regrowth is an incredible feat of natural engineering – one that Professor Alison Lloyd and her team at UCL have been studying in intricate detail for several years, funded in part by Cancer Research UK.
You might be wondering why a cancer charity would be funding research into nerve repair. But as well as helping understand this fundamental biological process, it also helps solve a vital and important puzzle: how cancer spreads through the body.
The team’s latest study has revealed how cells involved in nerve repair, known as Schwann cells, use blood vessels like biological ‘train tracks’ to migrate across the gap left when a nerve is damaged. And it looks as though some cancer cells may also go on the move in the same way.
Laying down tracks
When a nerve is cut, a number of different types of cells – including immune cells and repair cells known as fibroblasts – flood into the resulting gap, creating a kind of biological ‘mush’.
As we described in this post from 2011, special helper cells called Schwann cells are some of the first pioneers to make their way across this morass, forming solid ropes on which the delicate strands of the nerve cells (axons) can grow.
But these helper cells need a helping hand themselves. Although tests in the lab show that Schwann cells have the capacity to move around, they don’t know which direction to grow through the molecular mush. So they end up stuck, unable to go anywhere.
Clearly, something must be creating a path to help the Schwann cells find their way across the divide. But what?
The solution to this sticky situation, as Lloyd has now discovered, comes in the form of oxygen-sensing immune cells called macrophages. Publishing their findings in the journal Cell, she and her team found that macrophages could detect low levels of oxygen in the tissues on the far side of the nerve damage, sending out signals that attract new blood vessels to grow across the gap.
Like tracks for a train, these blood vessels act as guides for the Schwann cells, providing a smooth path across the mushy mess. And like a locomotive pulling along its carriages, the Schwann cells carry the nerve cells with them, repairing the damage and restoring nerve function.
It’s this process that can be seen in the picture above, created by layering together many images taken using a confocal microscope: the blood vessels are coloured blue, the Schwann cells are green while the fragile nerve axons are red.
So how does this relate to cancer?
Clues to cancer spread
Professor Lloyd’s results are shedding light on the ways in which all these different types of cells work together to repair nerve damage. And their research could lead to the development of better blood vessel-based ‘patches’ to help reconnect severed nerves. But they also have relevance to the way that some cancers spread through the body.
For a start, this latest study could explain how tumours that originate from Schwann cells – principally Schwannomas and neurofibromas – start to spread. Under the microscope, these tumours look a bit like unrepaired nerve damage, containing a mess of fibroblasts, blood vessels and immune cells. So understanding more about how Schwann cells go on the move, both in normal tissue and in tumours, might point towards new ways to treat these diseases in the future.
Then there’s the more general angle. It’s commonly believed that most cancers spread via the intricate network of blood vessels weaving their way around the body. But there are intriguing hints that some cancer cells – particularly those from invasive tumours that spread into or within the brain, such as glioma or melanoma – might crawl along blood vessel ‘tracks’, just like the Schwann cells do when they’re repairing nerves. We first wrote about this process back in 2009 in this post about research from our scientists in Oxford, and there’s also another interesting study on this from a team in the US.
Lloyd suspects that cancer cells are exploiting the normal nerve repair processes in order to spread in this way. She and her team are now searching for the molecular cues that Schwann cells use to find their way along blood vessels, as well as understanding more about how these biological pathways are laid down during repair and tumour growth.
In turn, this knowledge could one day help doctors sever these cellular escape routes, stopping cancer in its tracks.
A-L Cattin et al. Macrophage-Induced Blood Vessels Guide Schwann Cell-Mediated Regeneration of Peripheral Nerves. Cell (2015) in press. http://www.cell.com/cell/abstract/S0092-8674(15)00898-3