Most of the lives lost to cancer are due to secondary tumours, when the cancer spreads from one part of the body to another. Scientists have now discovered that cancer cells use different mechanisms to move around the body depending on their environment. This means that balanced combinations of different drugs, aimed at stopping the different types of movement, are needed to prevent cancer spreading.
The findings should help improve the efficiency of drug testing by allowing early tests to be done using the computational models developed by the team - which are faster and less expensive than laboratory experiments.
The research was carried out by Erik Sahai, Paul Bates, Melda Tozluoglu and their team at Cancer Research UK's London Research Institute (now part of the Francis Crick Institute).
Dr Tozluoglu explained: "For cancer to spread, cancer cells actually need to move inside the body, from one point to another, stop, and start a new tumour. Our work focuses on understanding how the cancer cells move in the body, so that we can stop them."
The researchers developed a computer model to mimic moving cancer cells and predict how they would move under different conditions. They started by measuring properties such as how much a cancer cell extends forward while 'crawling', or how much it can contract while 'squeezing'. They then created surroundings similar to inside the mice and tested how fast the model cell moved in these environments, as well as the effect of different drug treatments on the cell's movement. Finally, the team tested their results again in the laboratory, to prove the model was correct.
They found that when cancer cells move on top of smooth surfaces, they move most efficiently by 'crawling' on the surface. They take hold of the surface, extend forward and become elongated, and then detach themselves at the back, like moving in steps.
On the other hand, while moving through a complex meshwork such as structural connective tissue, cancer cells are more efficient if they are rounder and squeeze through the meshwork. Here, they do not need to stick to the rods of the meshwork but need contractile proteins, which contract the cell and help it squeeze through small gaps.
Dr Tozluoglu said: "Our study shows that cancer cells need different molecular mechanisms to navigate in different modes, just like you would need light running shoes to jog in the park but strong boots to hike in hills in the rain.
"We also know that cancer cells have the ability to use all different methods of movement, so stopping just one type will not stop them spreading through the body. In other words, if we take their hiking boots away, they will switch to running shoes and, although they may not be as fast, they will keep moving.
"We need to use drugs to target these different mechanisms in different environments - by eliminating sticking on a smooth surface and eliminating contractility in a complex meshwork. We need to apply balanced combinations of drugs to target both machineries."
The paper, Matrix geometry determines optimal cancer cell migration strategy and modulates response to interventions, is published inNature Cell Biology.
