Pathway to glioma?

Melissa Marino, Ph.D.
Published: February, 2007

The Hedgehog (Hh) signaling pathway plays a critical role in embryonic development and has been linked to a number of different types of cancer.

Researchers at Vanderbilt University Medical Center are now examining its role in one of the most fatal types of brain tumors—gliomas.

Gliomas are the most common type of primary brain tumors (meaning they arise in the brain and not from elsewhere in the body). These tumor cells resemble glia—cells in the brain that support and nourish the neurons, and some studies have suggested that an abnormality in the Hh pathway might be involved in their development.

Michael Cooper, M.D., assistant professor of Neurology, has teamed up with Reid Thompson, M.D., director of Neurosurgical Oncology, to examine Hh pathway activity in brain tumor samples stored in a tissue bank that Thompson established.

To date, they have found that the Hh pathway is activated in certain types of gliomas—those of intermediate grades II and III, but not in the most advanced grade IV tumors (known as GBMs, or glioblastoma multiforme). Importantly, they have found that the Hh pathway is activated in what appear to be progenitor or stem cell-like cells.

“Investigators have speculated for some time that grade IV gliomas may be different (than the others),” Cooper says. “This may suggest that not all stem cells—and not all cancer stem cells—would be the same.

“It’s a controversial idea,” he adds, “but our data suggest that grade IV gliomas may arise from a cell type that’s not Hh responsive, where grades II and III gliomas may arise from an Hh-responsive cell type.”

While the results suggest that Hh activity might someday be useful in predicting tumor behavior, the role of pathway activation in the tumor is not yet clear.

“It is guilt by association at this point,” Cooper says. “We still need to know what the pathway is doing. We think that it may have a role in tumor growth and invasion, but to determine that, we need a good animal model.”

While Cooper plans to develop an animal model, a Clinical Scientist Development Award he recently received from the Doris Duke Charitable Foundation will support a prospective clinical study to assess Hh pathway activity in gliomas that have been surgically removed from patients. Those patients will then be followed long-term.

“I’m a clinician, but my research has been at the basic science level,” he says. “So this award is taking (the research) to the next level, and it gives me a chance to learn a whole new set of skills.”

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