Bioelectric signals can be used to detect early cancer

February 1, 2013
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

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.

"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 " will be published in the May 2013 issue of " and Mechanisms" (available online on February 1).

Bioelectric signals underlie an important set of 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 such as , 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 in the frog embryos by injecting the samples with mRNAs () 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 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

Explore further: The face of a frog: Time-lapse video reveals never-before-seen bioelectric pattern

More information: 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

Related Stories

The face of a frog: Time-lapse video reveals never-before-seen bioelectric pattern

July 18, 2011
For the first time, Tufts University biologists have reported that bioelectrical signals are necessary for normal head and facial formation in an organism and have captured that process in a time-lapse video that reveals ...

Ovarian cancer cells hijack surrounding tissues to enhance tumor growth

September 4, 2012
Tumor growth is dependent on interactions between cancer cells and adjacent normal tissue, or stroma. Stromal cells can stimulate the growth of tumor cells; however it is unclear if tumor cells can influence the stroma.

Recommended for you

Team finds link between backup immune defense, mutation seen in Crohn's disease

July 27, 2017
Genes that regulate a cellular recycling system called autophagy are commonly mutated in Crohn's disease patients, though the link between biological housekeeping and inflammatory bowel disease remained a mystery. Now, researchers ...

Study finds harmful protein on acid triggers a life-threatening disease

July 27, 2017
Using an array of modern biochemical and structural biology techniques, researchers from Boston University School of Medicine (BUSM) have begun to unravel the mystery of how acidity influences a small protein called serum ...

CRISPR sheds light on rare pediatric bone marrow failure syndrome

July 27, 2017
Using the gene editing technology CRISPR, scientists have shed light on a rare, sometimes fatal syndrome that causes children to gradually lose the ability to manufacture vital blood cells.

Post-stroke patients reach terra firma with new exosuit technology

July 26, 2017
Upright walking on two legs is a defining trait in humans, enabling them to move very efficiently throughout their environment. This can all change in the blink of an eye when a stroke occurs. In about 80% of patients post-stroke, ...

Molecular hitchhiker on human protein signals tumors to self-destruct

July 24, 2017
Powerful molecules can hitch rides on a plentiful human protein and signal tumors to self-destruct, a team of Vanderbilt University engineers found.

Researchers develop new method to generate human antibodies

July 24, 2017
An international team of scientists has developed a method to rapidly produce specific human antibodies in the laboratory. The technique, which will be described in a paper to be published July 24 in The Journal of Experimental ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.