Scientists identifiy protein that seems to control the malignant features of brain tumor cells

Scientists from Wake Forest University School of Medicine have identified a protein that seems to control the malignant features of brain tumor cells, suggesting a new treatment target for anti-cancer drugs. The research is reported in the current issue of Molecular Cancer Research.

"This protein seems to be important in how cells acquire malignant characteristics and how they spread to healthy tissue," said Waldemar Debinski, M.D., Ph.D., director of the Brain Tumor Center of Excellence at Wake Forest University Baptist Medical Center. "It is very powerful and may be an attractive target for anti-cancer therapy."

The protein is also involved in late-stage breast, skin, colon and thyroid cancers, suggesting that a new treatment could apply to multiple cancers.

Debinski and colleagues identified the protein while studying glioblastomas, the most common form of brain tumor. Glioblastomas are considered the least curable of all human cancers. Like other tumors, glioblastomas require their own blood supply in order to grow and spread. The researchers' initial goal was to learn what controls this process.

But, when they measured levels of a protein that they thought might be involved, they found only very low levels. Instead, they discovered that a little-known protein – called Fra-1 – is present at large amounts in the tumor cells.

"We were very surprised when we saw it for the first time," said Debinski. "We had to learn more about Fra-1 because it is not a widely-studied biological factor."

What they learned got them interested in doing further research with Fra-1. For example, the protein is able to regulate a set of different genes.

Fra-1 is what is known as a transcription factor. It is one of many proteins that "reads" the genetic material in cells. If effect, transcription factors help control whether the instructions of genes are carried out by the cells.

Debinski and colleagues conducted several experiments to learn more about Fra-1's role in glioblastomas. They found that it makes the cancer cells more elongated, which might make it easier for them to infiltrate normal tissue. It also enables tumors to grow a blood supply. In addition, when non-tumor forming cells were supplied with Fra-1, they began producing tumors. On the other hand, when Fra-1 was eliminated from cells that were already tumor-producing, they stopped forming tumors.

"It is a powerful biological factor," said Debinski.

In their studies, the researchers found that more than 50 different genes seem to be affected by Fra-1, suggesting that its effects may be even broader than this initial study showed.

"We believe it may be good target for anti-cancer therapy, but we need to explore more," said Debinski.

The researchers suspect that Fra-1 works by partnering with other molecules. If they find that it's difficult to control the actions of Fra-1 with drug therapy, one of these other molecules might be more susceptible to treatment.

"Even if Fra-1 it not the ideal treatment target, I believe we're on the right track to identify one," said Debinski.

The research was funded in part by the Brain Tumor Center of Excellence. Debinski's research associate is Denise M. Gibo with Wake Forest Baptist, who contributed in a major way to the work on Fra-1 in brain tumors.

"She was the first to spot that Fra-1 is elevated in glioblastomas ," said Debinski.

The goal of the Brain Tumor Center of Excellence, which was formed in 2003, is to find better treatments – and one day a cure – for malignant brain tumors. In addition to its focus on research, the center provides a comprehensive program for patient care, and is the first center in the state to offer Gamma Knife stereotactic radiosurgery, a knifeless approach to brain surgery and radiation therapy.