In our increasingly connected and hectic world, the term “off-grid” has come to represent not only a self-sufficient lifestyle, but also a rejection of the status quo and many of the creature comforts that most are accustomed to.
We typically think of people going off-grid. You know the cliché – trade the comfortable nine-to-five in the city and cramped apartment for a solar-powered cabin on a rural plot of land, complete with a couple of goats and a handful of chickens.
While some of these characteristics of going off-grid may ring true, you’re likely not thinking about cancer cells ditching the rat race for an idyllic life in the country. But according to researchers in the UK, cancer cells can indeed go off-grid. And when they do, they’re not growing kale or making artisanal soaps. Off-grid cancer cells are plotting something much more sinister, and understanding their behavior could hold the key to stopping them.
Aggressive and Sophisticated Cancer Cells
Researchers from the Francis Crick Institute in London have discovered that some “particularly aggressive” lung cancer cells can develop their own electric network, not unlike what exists in the body’s nervous system, which could mean the cells are less dependent on the environment surrounding the tumor, allowing them to spread more easily.
The cells in question are from small cell lung cancer (SCLC), one of the most-difficult-to-treat types of cancer. SCLC is particularly challenging to treat because it is very aggressive and often spreads widely by the time it is diagnosed. For example, per the Cleveland Clinic, roughly 1 in 20 people with small cell lung cancer have tumors that haven’t spread beyond their lung.
The disease often recurs within two years of diagnosis, and the average five-year survival rate is around 7%.
The Discovery
Neuroscience techniques employed by the Crick Institute researchers enabled the discovery that SCLC cells have the ability to go off-grid and generate their own electrical activity, “building their own electrical network within the tumor, and becoming independent of the body’s main electrical supply, including the nerves surrounding the tumor.”
The team studied human and mouse SCLC samples, looking for electrical activity in order to determine whether the activity may offer clues into the aggressiveness of SCLC.
The Link Between Electrical Activity and Aggression…and Puffer Fish
Despite “having the same cancer-causing changes in their DNA,” the researchers noted that in mice, the non- Neuroendocrine (NE) cells did not spread and start tumors elsewhere in the body.
Neuroendocrine (NE) cells are nerve-like cells that produce hormones.
Next, the team needed to determine the impact of electrical activity in the NE cells. This process required a special ingredient – a dash of puffer fish.
Specifically, a toxin from puffer fish called tetrodotoxin (TTX), which suppresses electrical activity. The researchers found that TTX did not kill NE cells in a dish, but rather it, “reduced their potential to form tumors long-term, with no effect on non-NE cells.”
The team also studied molecular markers of increased electrical activity within a cohort of people with SCLC. They found that these markers were elevated in the cancer cells compared to adjacent healthy cells.
The researchers also found that as the cancer progressed, “non-NE cells showed markers suggesting they were increasingly pumping out lactate” – a distinct change in the fueling pattern of NE cells compared to most other cancer types that “can’t build their own electrical network.”
What it All Means
According to the researchers, their results suggest that the electrical activity of the NE cells is a key contributor to the tumor’s ability to grow and spread; a leading cause of cancer death in patients.
“Our work shows that NE cells in SCLC have the ability to go ‘off-grid’, starting to generate their own electrical supply, and also being fueled by supportive non-NE cells rather than the energy sources used by most other cells,” said Paola Peinado Fernandez, Postdoctoral Fellow and co-lead author on the study.
“We’ve identified a feature which makes these types of cancers more aggressive and harder to treat. We think that this acquired autonomy of cancer cells might free them from the dependency of their environment.”
Implications and Next Steps
According to the team at Crick, the study may offer valuable insights into the disease’s vulnerabilities and possible treatment.
“We knew that some cancer cells can mimic neural behavior, but we didn’t know how developing an independent electrical network might impact the development of disease. By combining neuroscience and cancer research techniques, we’ve been able to look at this disease from a different perspective,” said Leanne Li, Head of the Cancer-Neuroscience Laboratory at the Crick Institute.
“There’s still a long way to go to understand the biological impact of this electrical activity and the specific disease mechanisms that make the tumor more aggressive and harder to treat,” added Li. “But we hope that in understanding the way these cancer cells are fueled, we can also expose vulnerabilities that could be targeted with future treatments.”
Next, the research team plans to study the impact of electrical activity in other types of cancers, while also investigating potential treatment options associated with electrical activity in small cell lung cancer.
