By using machine learning and cutting-edge microscopes, scientists have uncovered what they believe to be a new form of communication between cancer cells. Described as a “type of electrical language,” the discovery may be key to the way cells within the same tumor work together to coordinate growth, and suggests breaking down these communications could offer new ways to treat the disease.
Shifts in electrical activity are known to take place in various cells in the human body, such as those in the heart that facilitate blood flow and the neurons that coordinate the many functions of the brain. Cells are also known to experience electrical changes when they become cancerous, with the surrounding cell membrane taking on a more positive charge that can promote their spread. The authors of this new study were able to tune into this electrical activity to gather some fascinating new insights.
“Of all the cells in the body, we usually associate ‘excitable’ brain or heart cells with electrical activity,” said study co-author Mustafa Djamgoz. “Our research suggests a hidden electrical signaling network among cancer cells that might play a key role in cancer cell behavior including communication with each other and other cells within the tumor. We know already that the spreading of cancer, the main cause of death from cancer, is facilitated by electrical activity.”
The work was led by scientists at Imperial College London and The Institute of Cancer Research, who used a microscope originally designed to observe electrical activity in brain cells. This was put to use on breast cancer cells in the lab and, to their surprise, the scientists found that the membrane voltage wasn’t just heightened, it appeared to fluctuate over time as it does in neurons.
Using machine learning, the team characterized the signals and assigned them into four categories such as noisy, blinking and waving. The team then used a drug to block sodium channels the cells rely on to generate the electrical signals, which in turn suppressed the fluctuating voltages.
"This is the first time we’ve been able to observe such rapid fluctuations in electrical activity within breast cancer cells,” said co-lead author Professor Chris Bakal, “It looks like breast cancer cells have established a type of electrical language. We still don’t know how complex the language is, but it could allow cancer cells to relay information about nearby nutrients or hostile environments across large distances, and ultimately promote tumor survival.”
In another round of experiments, the scientists took healthy cells and induced cancer in them, recording their electrical activity in both states. Once they had become cancerous, the cell membranes again displayed fluctuating voltages, though these varied across different cancer types. More aggressive cancers, for example, exhibited more frequent fluctuations.
“When healthy cells become cancerous, the changes they undergo can help them to grow and spread,” said co-lead author Dr Amanda Foust. “We know, for example, that certain genes that control cell multiplication can switch off, causing uncontrolled cell growth. We don't yet know why the voltage of membranes fluctuates in cancer cells – but our discovery and technology, enabled by the exciting collaboration of engineers and biologists, opens doors to further work that could help us better understand cancer signaling networks and growth.”
The scientists are now working to uncover the connections between these fluctuating voltages and the way cancer cells behave. Do certain forms of electrical activity correlate with the multiplication of cancer cells, or do some patterns signal it is time to slip away and attack other parts of the body? If these types of links can be established, scientists may be able to cut communications in a way that prevents the progression of the disease in different ways.
"If you can stop cancer cells communicating with one another, they could become easier to treat,” said Bakal. “It’s not so dissimilar from a war. If you can stop a commander from relaying information to soldiers at the front, the battle becomes easier to win.”
The research was published in the journal Communications Biology.
Source: The Institute of Cancer Research
