Breast cancer cells might have 'electrical language,' study claims

Imperial College of London's recent study has discovered that the membranes of breast cancer cells have varying voltages, providing information regarding their growth and dissemination. Collaborated with The Institute of Cancer Research, London, the study "could help us better understand how cancer cells ‘decide’ when to multiply and where to spread to," said in the press release.

This new study published in Communications Biology discovered that breast cancer cells behave a lot like neurons.

Several bioelectric abnormalities occur in cells as they develop cancer. For instance, the cell membrane, which surrounds cells, becomes more positively charged than healthy cell membranes.

The scientists defend that this might point to an electrical communication network between cancer cells that might one day be a target for disruption, leading to the development of potential new treatments.

“When healthy cells become cancerous, the changes they undergo can help them to grow and spread. We know, for example, that certain genes that control cell multiplication can switch off, causing uncontrolled cell growth," said Dr. Amanda Froust, co-lead author from the Imperial School of London's Department of Bioengineering.

“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.”

Electrical signals are blinking and waving

Eight breast cancer cell lines and one healthy breast cell line were used by the researchers to grow cells to evaluate the voltages. They used a microscope originally designed to capture electrical activity in brain cells to record the voltages of their cell membranes, and then they used machine learning to classify and characterize the signals.

The voltage of the cancer cell membranes was found to fluctuate. The electrical signals that appear to be "blinking" and "waving," though the additional investigation is required, may be cells communicating.

Tetrodotoxin, a strong neurotoxin that inhibits sodium channels to stop nerve cells from producing electrical charge, was added. Previous research has demonstrated that these sodium channels are necessary for the invasiveness of cancer cells.

They discovered that tetrodotoxin decreased the voltage fluctuations in cancer cells, much to how it affected nerve cells. According to the researchers, this may point to novel therapeutic approaches for preventing cancer cell behavior and communication.

"This is the first time we've observed such rapid fluctuations in electrical activity within breast cancer cells. 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," says co-lead author Professor Chris Bakal, Professor of Cancer Morphodynamics.

"Of all the cells in the body, we usually associate 'excitable' brain or heart cells with electrical activity. 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," added co-author Emeritus Professor Mustafa Camgöz at Imperial's Department of Life Sciences.

Abstract:

Cancer cells feature a resting membrane potential (Vm) that is depolarized compared to normal cells and expresses active ionic conductances, which factor directly in their pathophysiological behavior. Despite similarities to ‘excitable’ tissues, relatively little is known about cancer cell Vm dynamics. Here high-throughput, cellular-resolution Vm imaging reveals that Vm fluctuates dynamically in several breast cancer cell lines compared to non-cancerous MCF-10A cells. We characterize Vm fluctuations of hundreds of human triple-negative breast cancer MDA-MB-231 cells. By quantifying their Dynamic Electrical Signatures (DESs) through an unsupervised machine-learning protocol, we identify four classes ranging from "noisy” to “blinking/waving“. The Vm of MDA-MB-231 cells exhibits spontaneous, transient hyperpolarizations inhibited by the voltage-gated sodium channel blocker tetrodotoxin, and by calcium-activated potassium channel inhibitors apamin and iberiotoxin. The Vm of MCF-10A cells is comparatively static, but fluctuations increase following treatment with transforming growth factor-β1, a canonical inducer of the epithelial-to-mesenchymal transition. These data suggest that the ability to generate Vm fluctuations may be a property of hybrid epithelial-mesenchymal cells or those originated from luminal progenitors.