Bioelectric Signals Can Be Used to Detect Early Cancer
Investigators at Tufts University have discovered a bioelectric signal that can identify cells that are likely to develop into tumors. The researchers also found that they could lower the incidence of cancerous cells by manipulating the electrical charge across cells’ membranes. The researchers note that the voltage changes are not merely signs of cancer, but they control and direct whether or not cancer occurs. This work appears in a paper published in the journal Disease Models and Mechanisms.
Bioelectric signals underlie an important set of control mechanisms that regulate how cells grow and multiply. Michael Levin and graduate student Brook Chernet investigated the bioelectric properties of cells that develop into tumors in Xenopus laevis frog embryos.
In previous research, Dr. Levin and members of his laboratory have shown how manipulating membrane voltage can influence or regulate cellular behavior such as cell proliferation, migration, and shape in vivo, and be used to induce the formation or regenerative repair of whole organs and appendages. In this study, the researchers hypothesized that cancer can occur when bioelectric signaling networks are perturbed and cells stop attending to the patterning cues that orchestrate their normal development.
The researchers induced tumor growth in the frog embryos by injecting them with messenger RNA (mRNA) encoding human oncogenes Gli1, KrasG12D, and Xrel3. The embryos developed tumor-like growths that are associated with human cancers such as melanoma, leukemia, lung cancer, and rhabdomyosarcoma, a soft tissue cancer that most often affects children. When Dr. Levin and Ms. Chernet analyzed the tumor cells using a membrane voltage-sensitive dye and fluorescence microscopy, they discovered that the membrane voltage of tumor cells were depolarized relative to the surrounding tissue.
The Tufts researchers were also able to show that preventing membrane depolarization, by injecting the cells with mRNA for ion channels, inhibited tumor formation. Subsequent experiments showed that the cellular mechanism that allows hyperpolarization to inhibit tumor formation involved the transport of butyrate, a known tumor suppressor.
This work is detailed in a paper titled, “Transmembrane Voltage Potential is an Essential Cellular Parameter for the Detection and Control of Tumor Development.” This paper is available free of charge at the journal's Web site.