Researchers have discovered a particular type of cancer cell that relies on its own biological electric utility company to thrive. Disrupting this power plant – with the help of a puffer fish – showed a breakthrough way to fight the tumors.
Small cell lung cancer (SCLC) is a highly malignant and very aggressive type of cancer responsible for about 13% of all lung cancers. It is also sneaky. Typically, by the time the disease is diagnosed, it has already metastasized, making it extremely hard to treat.
Now, researchers from the Francis Crick Institute (FCI) have discovered that some of the cells involved with the formation of SCLC tumors demonstrate high levels of electrical activity. They've also determined the source of this power boost and say that using neurological drugs that typically disrupt electrical signals could be a powerful way to fight SCLC and, potentially, other tumors that operate in the same way.
"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," said study co-author Leanne Li, who is the head of the Cancer-Neuroscience Laboratory at FCI. "By combining neuroscience and cancer research techniques, we’ve been able to look at this disease from a different perspective."
Using mice engineered to have SCLC, the FCI researchers identified two types of cells involved in the disease: Neuroendocrine (NE) cells, which are similar to cells involved in the electrical activity of the nervous system, and non-neuroendocrine (non-NE) cells. Over time, the researchers found, cancer-activated gene expression caused some NE cells to turn into non-NE cells. What's more, they saw that the two types of cells began to work together, much in the same way neurons and supporting cells called astroglia work together in the nervous system.
Specifically, they found that the non-NE cells were shuttling lactate into the NE cells, functioning as an independent power supply to support their electrical activity. They also found that the more electrical activity the NE cells exhibited, the more aggressive the cancer was. They not only saw this effect in mice, but in humans suffering from SCLC as well.
"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 study co-lead author Paola Peinado Fernandez. "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."
Puffer fish to the rescue
With the deeper understanding of the electrical activity taking place in SCLC tumors, the researchers set out to see if they could disrupt it, and how that would impact the cancer's growth.
They exposed the cancer cells to a toxin from a puffer fish known as tetrodotoxin, which is known to suppress electrical activity. Sure enough, while the tetrodotoxin didn't kill the electricity-producing NE cells, it did reduce their potential to form tumors long-term, showing that interrupting the electrical activity of SCLC could be a powerful, breakthrough way to fight the disease.
The researchers are now looking at the electrical activity of other cancers, to see if they too exhibit similar properties to SCLC. If so, they might be susceptible to new treatment options that disrupt their growth by tamping down their electrochemical activity.
"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," said 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."
You can hear more about the research in the following video from FCI.
The research has been published in the journal Nature.
Source: The Francis Crick Institute
