Lab Studies Suggest New Approaches to Treating Gliomas

NEW ORLEANS—Basic science research efforts may be paying off in the understanding of malignant gliomas, potentially leading to treatments for this aggressive, deadly tumor, scientists reported at the Society for Neuroscience meeting.

Current treatments are few and ineffective, largely because of the ability of glioma cells to migrate into normal brain tissue. Secondary or metastatic brain tumors do not invade surrounding tissue and can respond to both surgical and chemotherapeutic modalities, while gliomas cannot.

Harald Sontheimer, PhD, of the University of Alabama at Birmingham, reported that a specific chloride ion channel protein, which he and his colleagues call glioma chloride channel (GCC), was present in all the biopsy samples from 24 glioma patients.

Ion channels are proteins that permit the movement of chloride ions across the membranes of brain cells. This type of chloride ion channel is not found in normal brain cells, Dr. Sontheimer said.

The investigators also found that almost all cells in the most aggressive gliomas, glioblastomas, contained GCC, compared with only half the cells in the more slowly growing astrocytomas. This suggests that the protein may be involved in the spread of glioma cells, he said.

They then looked for a molecule that would bind with GCC and kill the targeted cancerous cells. They found that the giant yellow Israelian scorpion (see photographs) is a rich source for molecules that bind to ion channels, and they were able to engineer similar molecules to target cancer cells. In vitro, these molecules sought out the glioma chloride channel, bound to the cancer cells, and killed them, Dr. Sontheimer reported. The research team is now applying this approach in an animal model.

Yale University researchers reported that it may be possible to inhibit the spread of gliomas in the brain by targeting a protein that helps glioma cells migrate from one area of the brain to another. The protein, dubbed BEHAB (brain-enriched hyaluronan), is one of many molecules located in the extracellular matrix and is found only in the brain.

BEHAB is expressed at unusually high levels in invasive brain tumors but not in any other kind of tumor, reported Susan Hockfield, PhD, a neurobiologist at Yale.

“Our experiments suggest that BEHAB endows tumor cells with their unusual ability to migrate into normal brain tissue,” she said. “We are currently trying to develop methods that could block the protein either from being made or from functioning, with the aim of slowing the migration of tumor cells.”