The research, led by investigators at Bart’s Cancer Institute and by researchers at Queen Mary University of London and King’s, suggests that altering this change can reduce tumor cell invasion. The team also identified a key molecule that drives this process, which could be the key to future therapies to stop the spread of cancer.
The ability of cancer cells to break away from the original tumor and spread to other parts of the body, known as metastasis, is responsible for most cancer deaths. Currently it is not well understood and therefore very difficult to treat.
The study was led by Victoria Sanz-Moreno, professor of cancer cell biology at Queen Mary University of London, who began the research while at King’s Randall Center for Cell and Molecular Biophysics.
“We still don’t target secondary disease enough in the clinic, and I think this needs to change. In our lab, we want to understand: What are the characteristics of cells that can metastasize? What are their weaknesses? And how do we target them?
Professor Victoria Sanz-Moreno, Queen Mary University of London
Melanoma skin cancer is one of the fastest growing cancers. If melanoma is diagnosed at an early stage before it has spread, almost all patients in the UK will survive the disease for a year or more. But once the disease has spread, this survival rate is cut in half.
In the new study, published in Nature Communications, the team looked at migrating tumor cells. They found that metastasizing tumor cells adopt a style of motility where the cells maintain a loose connection with their surroundings, enabling them to slide through tissues. This requires much less energy than the common style of cell motility in which cells cling to their surroundings and drag themselves through their surroundings.
They observed that invasive tumor cells adapted their mitochondria — the cellular powerhouses that produce energy for the body — to their efficient movement style adopted during migration. Tumor cells select for small, fragmented mitochondria that operate in a low-power mode. This contrasts with non-invasive cells that have large branched networks of mitochondria operating in high-power mode.
The team found that if they manipulated the shape of mitochondria in metastasizing tumor cells and forced them to aggregate more, the cells lost their aggressive behavior. Similarly, if they disrupt mitochondria more than in non-invasive cells, the cells start to act like they are metastasizing tumor cells. The researchers found that a molecule called AMPK sits at the center of these processes. It senses the cell’s energy needs and controls the cytoskeleton, which determines the cell’s movements and behavior.
A team from King’s, led by Shashi Conte, professor of structural biology at the Randall Center, collaborated with Professor Sanz-Moreno’s research group throughout the study. Professor Conde used the NMR metabolomics facility to analyze the metabolism of several melanoma cells with different malignancies.
We are excited to be able to use our metabolomics expertise in the core NMR facility to understand how cancer cells behave and their potential to metastasize.
Shashi Conde is professor of structural biology and director of the Randall Center
A researcher at the Randall Center and School of Cardiovascular and Metabolic Medicine & Sciences, Dr. Mark Holt developed bespoke Wolfram language code to analyze the movement of cancer cells through a 3D collagen matrix.
Patients with advanced cancer often face difficult treatments and poor survival prospects. These insights into how cancer cells travel throughout the body could be incredibly valuable for designing interventions to prevent it in the future. The more we know about what happens in the body of cancer patients, the better our ability to cope with it.
Professor Ketan Patel, Chief Scientist at Cancer Research UK