Potential "electrical language" for breast cancer cells

New research has found variable voltages present on breast cancer cells' cell membranes, revealing how
they grow and spread.

The study, led by Imperial College London and the Institute for Cancer Research in 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 bioelectric changes
.
For example, the cell membrane that surrounds the cell carries more positive charge
than the healthy cell membrane.

The new study, published in the journal Communications Biology, found that breast cancer cells not only have higher membrane voltages than healthy cells, but also fluctuate over time — breast cancer cells behave much like neurons
.
The researchers believe this could indicate that the electronic communication network between cancer cells could be targeted for destruction 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
.
For example, we know that certain genes that control cell proliferation shut down, causing cell growth to spiral out of control
.
We don't yet know why the voltage of cell membranes in cancer cells fluctuates, but our findings and techniques, with exciting collaborations of engineers and biologists, open the door to further work that could help us better understand cancer signaling networks and growth
.
" ”

Test the network

To test the voltage, the researchers cultured cells from 8 breast cancer cell lines and 1 healthy breast cancer cell line
.
They then recorded the voltage of the cell membrane with a microscope, originally designed to record the electrical activity of brain cells, and then used machine learning to classify and characterize
the signals.

Unexpectedly, they found fluctuations in the cell membrane voltage of cancer cells
.
While more research is needed, researchers suspect that the "blinking" and "wiggling" electrical signals may be a form of
communication between cells.

They added tetrodotoxin, a powerful neurotoxin that blocks sodium ion channels and prevents nerve cells from generating electrical charges
.
Previous studies have shown that cancer cells rely on these sodium channels to become more aggressive
.

They found that, just like it did on nerve cells, tetrodotoxin suppressed voltage fluctuations
in cancer cells.
The researchers say this could point to new therapeutic avenues
for blocking cancer cells' communication and behavior.

Professor Chris Bakal, professor of cancer morphological dynamics at the Institute of Cancer Research in London and co-lead author of the study, said: "This is the first time we have observed such rapid fluctuations
in electrical activity within breast cancer cells.
It looks like breast cancer cells have built up an electrical language
.
We still don't know how complex this language is, but it allows cancer cells to relay information about nearby nutrients or harsh environments over long distances, and ultimately promote tumor survival
.
”

To further validate their findings, they induced cancer in healthy cell lines and then recorded them
again.
They found that once these cells became cancerous, the voltage of their membranes also fluctuated
.

Different cancer types have different levels of electrical signals
.
The more aggressive and incurable the cancer cell lines have more frequent fluctuations, and signals sometimes travel
from cell to cell in the form of waves.

Study co-author Mustafa Djamgoz, Emeritus Professor in the Department of Life Sciences at Imperial College London, said: "Of all the cells in the human body, we usually associate
'excitable' brain or heart cells with electrical activity.
Our research shows that there is a hidden network of electrical signals between cancer cells, which may play a key role in the behavior of cancer cells, including communication
between cancer cells and between other cells within the tumor.
We already know that the spread of cancer, the leading cause of cancer death,
is facilitated by electrical activity.
”

Professor Bakal added: "We think these networks can even enable cancer cells to form brain-like structures, allowing cancer cells to act
together as a machine rather than as a single unit.
"

Connect the threads

The researchers are now working to identify and break down potential links between cell membrane voltage and cancer cell behavior to see if they can be cut off
.
Professor Bakal said: "If you can stop communication between cancer cells, they become easier to treat
.
This is no different from
war.
If you can stop the commander from delivering information to the frontline soldiers, the battle will be easier to win
.
”

Dr Foust said: "We are now investigating the role of
voltage in cancer cell behaviour.
Do cancer cells clon and proliferate when the voltage fluctuates in a certain pattern? Or will it disconnect and invade other parts of the body? Can we use this knowledge to intervene at specific stages of tumor fluctuations to prevent cancer from spreading? These are key questions
that we hope to answer through ongoing work.
”

Peter Quicke, Yilin Sun, Mar Arias-Garcia, Melina Beykou, Corey D.
Acker, Mustafa B.
A.
Djamgoz, Chris Bakal, Amanda J.
Foust.
Voltage imaging reveals the dynamic electrical signatures of human breast cancer cells.
Communications Biology, 2022; 5 (1)