Biologists at Tufts University School of Arts and Sciences 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.
This shows a tumor within a tadplole embryo that has been labeled with red fluorescence to allow tracking. Credit: Brook Chernet; Tufts University School of Arts and Sciences
"The news here is that we've established a bioelectric basis for the early detection of cancer," says Brook Chernet, doctoral student and the first author of a newly published research paper co-authored with Michael Levin, Ph.D., professor of biology and director of the Center for Regenerative and Developmental Biology.
Levin notes, "We've shown that electric events tell the cells what to do. The voltage changes are not merely a sign of cancer. They control and direct whether the cancer occurs or not."
Their paper, "Transmembrane Voltage Potential is an Essential Cellular Parameter for the Detection and Control of Tumor Development" will be published in the May 2013 issue of "Disease Models and Mechanisms" (available online on February 1).
Bioelectric signals underlie an important set of control mechanisms that regulate how cells grow and multiply. Chernet and Levin investigated the bioelectric properties of cells that develop into tumors in Xenopus laevis frog embryos.
In previous research, Tufts scientists 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.
Tumor Cells Exhibit a Bioelectric Signature
The researchers induced tumor growth in the frog embryos by injecting the samples with mRNAs (messenger RNA) encoding well-recognized 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 the researchers analyzed the tumor cells using a membrane voltage-sensitive dye and fluorescence microscopy, they made an exciting discovery. "The tumor sites had unique depolarized membrane voltage relative to surrounding tissue," says Chernet. "They could be recognized by this distinctive bioelectric signal.
Changing Electrical Properties Lowers Incidence of Tumors
The Tufts biologists were also able to show that changing the bioelectric code to hyperpolarize tumor cells suppressed abnormal cell growth. "We hypothesized that the appearance of oncogene-induced tumors can be inhibited by alteration of membrane voltage," says Levin, "and we were right."
To counteract the tumor-inducing depolarization, they injected the cells with mRNA encoding carefully-chosen ion channels (proteins that control the passage of ions across cell membranes).
Using embryos injected with oncogenes such as Xrel3, the researchers introduced one of two ion channels (the glycine gated chloride channel GlyR-F99A or the potassium channel Kir4.1) known to hyperpolarize membrane voltage gradients in frog embryos. In both cases, the incidence of subsequent tumors was substantially lower than it was with embryos that received the oncogene but no hyperpolarizing channel treatment.
Experiments to determine the cellular mechanism that allows hyperpolarization to inhibit tumor formation showed that transport of butyrate, a known tumor suppressor, was responsible
The research was supported by grants from the National Institutes of Health (awards AR061988, AR055993) and the G. Harold and Leila Y. Mathers Charitable Foundation.
Chernet, B. T. and Levin, M. (2013). Transmembrane voltage potential is an essential cellular parameter for the detection and control of tumor development in a Xenopus model. Dis. Model. Mech. 8 February [Epub ahead of print] doi:10.1242/dmm.010835
Tufts University, located on three Massachusetts campuses in Boston, Medford/Somerville, and Grafton, and in Talloires, France, is recognized among the premier research universities in the United States. Tufts enjoys a global reputation for academic excellence and for the preparation of students as leaders in a wide range of professions. A growing number of innovative teaching and research initiatives span all Tufts campuses, and collaboration among the faculty and students in the undergraduate, graduate, and professional programs across the university's schools is widely encouraged.
Alex Reid | EurekAlert!
Antioxidants cause malignant melanoma to metastasize faster
09.10.2015 | University of Gothenburg
Finding cannabinoids in hair does not prove cannabis consumption
07.10.2015 | Universitätsklinikum Freiburg
Nondestructive material testing (NDT) is a fast and effective way to analyze the quality of a product during the manufacturing process. Because defective materials can lead to malfunctioning finished products, NDT is an essential quality assurance measure, especially in the manufacture of safety-critical components such as automotive B-pillars. NDT examines the quality without damaging the component or modifying the surface of the material. At this year's Blechexpo trade fair in Stuttgart, Fraunhofer IZFP will have an exhibit that demonstrates the nondestructive testing of high-strength automotive body parts using 3MA. The measurement results are available in a matter of seconds.
To minimize vehicle weight and fuel consumption while providing the highest level of crash safety, automotive bodies are reinforced with elements made from...
The MICADO camera, a first light instrument for the European Extremely Large Telescope (E-ELT), has entered a new phase in the project: by agreeing to a Memorandum of Understanding, the partners in Germany, France, the Netherlands, Austria, and Italy, have all confirmed their participation. Following this milestone, the project's transition into its preliminary design phase was approved at a kick-off meeting held in Vienna. Two weeks earlier, on September 18, the consortium and the European Southern Observatory (ESO), which is building the telescope, have signed the corresponding collaboration agreement.
As the first dedicated camera for the E-ELT, MICADO will equip the giant telescope with a capability for diffraction-limited imaging at near-infrared...
Self-driving cars will be on our streets in the foreseeable future. In Graz, research is currently dedicated to an innovative driver assistance system that takes over control if there is a danger of collision. It was nature that inspired Dr Manfred Hartbauer from the Institute of Zoology at the University of Graz: in dangerous traffic situations, migratory locusts react around ten times faster than humans. Working together with an interdisciplinary team, Hartbauer is investigating an affordable collision detector that is equipped with artificial locust eyes and can recognise potential crashes in time, during both day and night.
Inspired by insects
An interdisciplinary team of researchers has built the first prototype of a miniature particle accelerator that uses terahertz radiation instead of radio...
At present, tiny magnetic whirls – so called skyrmions – are discussed as promising candidates for bits in future robust and compact data storage devices. At...
01.10.2015 | Event News
30.09.2015 | Event News
17.09.2015 | Event News
09.10.2015 | Information Technology
09.10.2015 | Materials Sciences
09.10.2015 | Life Sciences