New research has found varying tensions in the membranes of breast cancer cells, revealing clues about how they grow and spread.
The research, led by Imperial College London and the Institute of Cancer Research, London, could help us better understand how cancer cells ‘decide’ when to multiply and where to spread.
When cells become cancerous, they undergo a series of bioelectrical changes. For example, the layer surrounding cells, called the cell membrane, becomes more positively charged than healthy cell membranes.
This new research, published today in Communications Biology, found that membrane tension is higher than in healthy cells, but also fluctuates over time, with breast cancer cells behaving like neurons. Researchers believe this could point to an electrical communication network between cancer cells that could be a target for disruption in the future, creating possible new treatments.
Co-lead author Dr Amanda Foust, from Imperial’s Department of Bioengineering, said: “When healthy cells become cancerous, the changes they undergo can help them grow and spread. We know, for example, that certain genes that control cell multiplication can switch off, causing uncontrolled cell growth.
“We don’t yet know why membrane tension fluctuates in cancer cells – but our discovery and technology, made possible by the exciting collaboration of engineers and biologists, opens the door to further work that could help us better understand cancer signaling networks and their growth.”
Test the network
To test the strains, the researchers cultured cells from eight breast cancer cell lines and one healthy breast cell line. They then recorded the voltages of their cell membranes with a microscope originally designed to film electrical activity in brain cells, before using machine learning to categorize and characterize the signals.
Unexpectedly, they discovered fluctuations in the voltage of cancer cell membranes. Although more research is needed, researchers suspect that the “flashing” and “rippling” electrical signals could be a form of communication between cells.
They added tetrodotoxin, a potent neurotoxin that blocks sodium channels to prevent the generation of electrical charges in nerve cells. Previous studies had shown that cancer cells rely on these sodium channels to become more invasive.
They found that, similar to its effect on nerve cells, tetrodotoxin suppressed voltage fluctuations in cancer cells. The researchers say this could potentially point to new treatment pathways to block cancer cell communication and behavior.
Co-lead author Professor Chris Bakal, Professor of Cancer Morphodynamics at the Institute of Cancer Research, London, said: “This is the first time we have seen such rapid fluctuations in electrical activity in breast cancer cells. It looks like breast cancer cells. have established a type of electrical language. We still don’t know how complex language is, but it could allow cancer cells to relay information about nearby nutrients or hostile environments over great distances, and ultimately aid tumor survival.
To further test their findings, they induced cancer in the healthy cell line before recording them again. They found that once these cells became cancerous, the tension in their membranes also fluctuated.
The level of the electrical signals varied according to the types of cancer. The more aggressive and incurable cancer cell lines showed more frequent fluctuations, with the signals sometimes appearing as a wave moving from cell to cell.
Co-author Professor Emeritus Mustafa Djamgoz from Imperial’s Department of Life Sciences said: “Of all the cells in the body, we generally associate ‘excitable’ brain or heart cells with electrical activity. Our research suggests a hidden electrical signaling network among cancer cells that may play a key role in cancer cell behavior, including communication with each other and with other tumor cells.We already know that cancer spread , the leading cause of cancer death, is facilitated by electrical activity.
Professor Bakal added: “We think these networks may even allow cancer cells to form brain-like structures that allow cancer cells to act together as a single machine, rather than as individual units.”
Connect the clues
Researchers are now working to identify and untangle potential links between cell membrane tension and cancer cell behavior, to see if they can be severed. Professor Bakal said: “If you can stop cancer cells from communicating with each other, they might become easier to treat. It’s not that different from a war. If you can stop a commander from passing information to soldiers at the front, the battle becomes easier to win.”
Dr Foust said: “We are currently studying the role of voltage in the behavior of cancer cells. Do cancer cells clone and multiply when their voltage fluctuates in a certain pattern, or rupture to invade from other parts of the body? Can we use this knowledge to intervene at a particular stage of fluctuation to prevent the spread of cancer? These are key questions that we hope to answer through our ongoing work.
This study was funded by Integrated Biological Imaging Network, Royal Academy of Engineering, Biotechnology and Biology Research Council (BBRC, part of UKRI), Wellcome Trust, Engineering and Physical Sciences Research Council (EPSRC, part of UKRI), Cancer Research UK and Stand Up to Cancer UK.