The Sequence 2/17-2/23
The Electric Role of Neuroendocrine Cells in Cancer Progression
The Electric Role of Neuroendocrine Cells in Cancer Progression
This study discusses the relationship between neuroendocrine cells (NE), cells that are like nerve cells but also make hormones like cells of the endocrine system, and cancer progression. In the study, researchers observed mice engineered to have Small-cell lung cancer (SCLC) and identified two types of cells involved in the disease: NE cells and non-NE cells. Although previous studies have shown that both elevated levels of neuronal receptors as well as the expression of neuronal receptors in cell types where they’re not normally present promote tumor progression in many cancer types, the role that electrical excitability plays has remained unclear. This study expanded the scope by comparing the ways NE and non-NE cells act as drivers of tumor evolution.
What did the study find about the role of NE cells and cancer progression?
Let’s start with understanding NE cells. NE cells, similar to neurons, are excitable and capable of firing action potentials. This is possible because the cells have the sodium and potassium voltage-gated channel currents necessary for action potential firing. Now, this is where SCLC comes in: SCLC cells are predominantly pulmonary neuroendocrine cells (PNECs) and are electrically active, making them prime test subjects for studying the metastatic potential of SCLC.
After characterizing the electrophysiological properties of both human and mouse SCLC cell lines, the researchers found that the more electrical activity the NE cells exhibited, the more aggressive the cancer was. The effect was evident in both mice and humans. Not only that, they noticed the non-NE cells were shuttling lactate into the NE cells, supporting their electrical activity. Results showed that NE cells have the ability to not only generate their own electrical supply, but also to be fueled by supportive non-NE cells. The fact that the NE cancer cells are able to produce their own energy and borrow energy from sources other cells cannot ultimately render them more aggressive and harder to treat.
How does this affect individuals with cancer?
In addition to studying how NE cells affect cancer progression, the group studied a potential cancer treatment that suppresses electrical activity. They exposed the cancer cells to a toxin from a puffer fish known as tetrodotoxin, which is known to suppress electrical activity. Turns out, the tetrodotoxin treatment reduced the potential of the NE cells to form tumors long-term. This showed that interrupting the electrical activity of SCLC could be a potential treatment to fight the disease. More research needs to be done on the efficacy of tetrodotoxin, and this particular group of researchers is looking to study the electrical activity of other cancers to see if they exhibit similar properties to SCLC. According to cancer biologist and co-author Leanne Li, "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… 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”. Li explained they might even respond to drugs that are used to treat neurological conditions.
What’s the takeaway?
Researchers studied the neuron-like cells called NE cells, which function similarly to cells involved in the electrical activity of the nervous system, in mice and humans with SCLC. They found the cells rely not only on their own biological electric utility to thrive, but that supporting cells provide the NE cells with lactate as a fuel source. The study confirmed SCLC is more aggressive when it is highly electrically active, and took steps to show that its growth can be suppressed by blocking this electrical activity. As SCLC growth relies on electrical activity, NE cancer cells may be susceptible to new treatment options that disrupt their growth by tamping down their electrochemical activity in the future.
https://www.nature.com/articles/s41586-024-08575-7
https://cancer.ca/en/cancer-information/cancer-types/neuroendocrine-tumours/what-are-neuroendocrine-tumours/the-neuroendocrine-system
https://pmc.ncbi.nlm.nih.gov/articles/PMC8524104/
https://newatlas.com/cancer/cancer-power-supply/
https://theweeklysequence.substack.com/p/the-sequence-124-1210