Brain tumors coax important support from nearby immune system cells

g cells' effects on brain tumors, Gutmann turned to NF1, which affects more than 100,000 people in the United States. Gutmann has studied the condition for years both to help improve NF1 treatment and to develop insights into brain tumors generally. As a part of that research, his lab developed a mouse model of NF1.

Brain tumors in human patients and in the mouse model arise from brain support cells known as astrocytes. To begin the new study, Gutmann and his postdoctoral fellow Girish C. Daginakatte, Ph.D., studied these brain tumors early in their development to see if any other cell types were consistently nearby. They found microglia, a cell type they had previously noted in human tumor samples.

Microglia are similar to monocytes, immune system cells that circulate throughout the body. Scientists are still debating the role of microglia. "I think people recognize now that microglia can be both good guys and bad guys," Gutmann says. "We've shown that they can definitely be subverted into a bad guy role by tumors."

When researchers gave the mice drugs that dampen immune system function, blocking activation of the microglia, tumor growth slowed. To get a sense for what the microglia was making that boosts tumor growth, they compared the proteins produced by microglia from the mouse model and microglia from normal mice.

Among other differences, microglia from the mouse model made more of an enzyme called hyaluronidase. Other scientists had previously identified hyaluronidase as a contributor to processes that trigger healing and regrowth after brain and spinal cord injury. In a series of test tube experiments, Gutmann showed that hyaluronidase can promote astrocyte growth, and that inhibiting microglia production of hyaluronidase slowed their growth-promoting effects.

"Now we have to wait for pharmaceutical scientists to develop inhibitors of hyaluronidase activity that can be used as potential treatments," Gutmann says. "In the mean

Contact: Michael C. Purdy
Washington University School of Medicine

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