Breast cancer cells might have ‘electrical language,’ study claims

The new findings could aid in breast cancer treatment.

A recent study by Imperial College of London found that breast cancer cells’ membranes have different voltages. This information can be used to determine their growth and spread. stated in a press release that the study was done in collaboration with The Institute of Cancer Research (London). It “could help improve our understanding of how cancer cells ‘decide’ when and where they should spread.”

The new study, published in Communications Biology, found that breast cancer cells behave very much like neurons.

As cells develop cancer, there are a variety of bioelectric abnormalities. The cell membrane surrounding cells becomes more positively charged than the healthy cell membranes.

Scientists defend this finding as pointing to an electrical communication system between cancer cells, which could one day be a target for disruption. This may lead to the development of possible new treatments.

“When cancerous cells develop from healthy cells, the changes that they go through can allow them to grow and spread. For example, we know that some genes that control cell multiplication may switch off, which can lead to uncontrolled cell growth,” Dr. Amanda Froust from the Imperial School of London’s Department of Bioengineering.

“We don’t know the reason the voltage of membranes fluctuates within cancer cells. However, our discovery and technology enabled by the exciting collaboration between engineers and biologists opens doors for further research that could help us better understand the signaling networks and cancer growth.”

Electrical signals are blinking and waving

Researchers used eight breast-cancer cell lines as well as one healthy breast cell to grow cells for evaluating the voltages. The researchers used a microscope that was originally intended to record electrical activity in brain cells to determine the voltages. They then used machine learning to classify the signals and to characterize them.

It was discovered that the voltage in cancer cell membranes fluctuated. Although the electrical signals appear to be “blinking” or “waving”, additional investigation is necessary to determine if these signals are actually cells communicating.

Tetrodotoxin was added to the mixture. This neurotoxin inhibits sodium channels and stops nerve cells from producing electric charge. These sodium channels have been shown to be essential for the invasion of tumor cells.

Researchers discovered that tetrodotoxin reduced voltage fluctuations in cancer-cell cells similar to nerve cells. Researchers believe this could lead to new therapeutic approaches to prevent cancer cell behavior or communication.

“This is the first observation of such rapid fluctuations in the electrical activity within breast carcinoma cells. It appears that breast cancer cells have developed an electrical language. Although we don’t yet know the complexity of this language, it could enable cancer cells to communicate information about nearby nutrients and hostile environments over large distances, which could ultimately lead to tumor survival,” Professor Chris Bakal, co-lead author, Professor Cancer Morphodynamics.

“Of all cells in the body we often associate the ‘excitable brain’ or heart cells with electrical activity. Our research has shown that there is an electrical signaling network hidden within cancer cells. This network may play a crucial role in the behavior of cancer cells, as well as communication between them and other tumor cells. “We know that electrical activity facilitates the spread of cancer. This is the primary cause of death.” said Mustafa Camgoz, Emeritus Professor at Imperial’s Department of Life Sciences.

Abstract:

Cancer cells have a resting membrane potential, or Vm, that is significantly lower than normal cells. It also expresses active conductances which are directly involved in their pathophysiological behavior. Although there are similarities between cancer cells and ‘excitable tissues, very little information is available about cancer cell Vm dynamics. High-throughput, cell-resolution Vm imaging shows that Vm fluctuates dynamically within breast cancer cells compared to MCF-10A non-cancerous cells. Vm fluctuations in hundreds of triple-negative human breast cancer MDAMB-231 cells are analyzed. We identified four types of Vm fluctuations by quantifying Dynamic Electrical Signatures through an unsupervised machine learning protocol. These classes range from “noisy to blinding/waving”. MDA-MB-231 cells’ Vm shows spontaneous, transient hyperpolarizations that are inhibited by the voltage–gated sodium channel blocker tetrodotoxin and calcium-activated potassium channels inhibitors apamin or iberiotoxin. The Vm of MCF-10A cells is comparatively static, but fluctuations increase following treatment with transforming growth factor-b1, 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.

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