An electrical switch for cancer?

Biologists have identified a new cell type in vertebrates that remotely mediates the transformation of stem cells into either healthy skin cells or cancerous melanoma, providing a potential new tool for researchers in both oncology and regeneration biology.

A model of melanocyte control
by transmembrane potential of
remote "instructor cells".
Image: Disease Models and Mechanisms.
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In a paper published Tuesday (19 October) in Disease Models and Mechanisms, the researchers, led by linkurl:Michael Levin;https://ase.tufts.edu/faculty-guide/fac/mlevin11.biology.htm of Tufts University, describe how, by manipulating the voltage across the cell membranes of these so-called "instructor cells" in frog tadpoles in vivo, they have been able to dictate the fate of the descendants of neural crest stem cells "with exquisite specificity." De-polarizing the cells led to aggressive, metastatic melanoma. A similar effect was found in human pigment cells in vitro.The instructor cells themselves lie outside of the neural crest, but appear to communicate with the stem cell population via a long-range signal based on serotonin. Levin told The Scientist that, while the idea that the electrical state of cells is involved in the formation of tumors is not a new one, his study shows that the electrical properties of one type of cell can induce other, distant cells to change their behavior, and might be "a key switch that mediates the stem cell-cancer cell distinction."Regeneration and cancer are widely regarded as flipsides of the same coin -- raising concerns stem cell therapy could lead to cancer, for instance. The latest finding "has delineated new very early steps in both regeneration and transformation from stem cell to tumor cell revealing another unknown role of serotonin, said linkurl:Ido Kema,;https://www.nvkc.nl/scripts/organisatie/adressenleden.php?zoeklid=K0011&nr=true who works on serotonin-related cancers at University Medical Center Groningen, Netherlands. The research is "really excellent work," Kema, who was not involved in the study, added in an email.Previous research has already demonstrated the importance of electricity in regeneration. For instance, Levin and his colleagues found that amputated tadpole tails can be linkurl:induced to regenerate;https://www.the-scientist.com/news/display/52918/ by application of an electrical current across the wound. But linkurl:Richard Borgens,;https://www.vet.purdue.edu/cpr/ a regenerative biophysicist at Purdue University, where he directs the Center for Paralysis Research, said these results may not apply to all types of cancers. Specifically, he said he suspects that regeneration-gone-awry may be behind a specific subset of neoplasms, but many others have different triggers. "They don't have any part in this story." Still, he added, the instructor cell "is a really neat idea." Levin noted that these particular instructor cells communicate only with the melanocyte-melanoma system. "That's unbelievable specificity," he said -- and if these cells exist, surely there are instructor cells that are speaking to other cell types. "The interesting thing now is to look for more, different kinds of instructor cells, because by learning this bioelectrical language by means of which they communicate, we might be able to change cell behavior in beneficial ways, for applications in birth defects, cancer, and regenerative medicine."D. Blackiston et al, "Transmembrane voltage gradient in GlyCl-expressing cell population controls behavior of neural crest derivatives in vivo," Disease Models and Mechanisms, 2010. doi:10.1242/dmm.005561, 2010.
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