Work we’re funding as part of our Quest for Cures research has recently been published in the prestigious scientific journal Nature Communications. And excitingly it’s been chosen as an Editor’s Highlight feature article in the Stem Cell section.
Professor Steve Pollard at the University of Edinburgh has done a detailed study of a group of normal brain cells called the neural stem cells (NSCs). Stem cells are important because they can turn into different types of cells, and one theory is that they can cause tumours.
The relevance of these cells in glioblastoma research is because, as Professor Pollard tells us in his article, “GBMs are driven by cells with NSC characteristics”. This means that while chemotherapy is targeting active GBM cells, there could be a supply of ‘sleeping’ cells primed to regrow the tumour as soon as the therapy stops.
Neural stem cells naturally exist in the brain in a quiescent (or sleeping) state. If they are needed for repair or regeneration they are activated by chemical signals. Professor Pollard’s research has shown that this is not just an on/off switch, but that some NSCs are genetically ‘primed’ to come out of quiescence.
They did lots of experiments to show that the NSCs are in three different states: deep quiescence; primes/shallow quiescence; and activate/ proliferating. They were also able to make the cells switch between these stated by changing the growth media (nutrients) the cells were grown in.
By analysing what changed in the cells between different states they found a key interaction that they think holds the NSCs back from becoming active.
One of the chemicals that can cause the NSCs to wake up is called the epidermal growth factor receptor (EGFR). A key new piece of information that Professor Pollard has discovered is about the control of EGFR by a protein called LRIG1 (shown in red in the image above).
In NSCs with LRIG 1, more EGFR didn’t activate the cell, but effectively primed it to start dividing. (Think of a car, the EGFR is the accelerator and LRIG1 is like the clutch… When LRIG1 is in play the EGFR can build up ready for a speedy start, but the engine doesn’t engage.)
This promising research is in the discovery phase. Next the team will be looking at glioblastoma cells specifically and looking for LRIG1. They hypothesise that high LRIG1 could mean that quiescent tumour cells can wake up more easily and start growing again.
In the long term we hope that knowing more about how some tumours escape therapy, and start to regrow quickly, will give our researchers new targets to stop brain tumours in their tracks.
Find out more about work we’re funding in Professor Pollard’s lab here.