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Bioelectric signals can be used to detect early cancer
Date:1/31/2013

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


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Contact: Alex Reid
alexander.reid@tufts.edu
617-688-2753
Tufts University
Source:Eurekalert  

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