Studying “triple threat” protein could lead to new brain cancer treatments

Written by 
Jessica Moore
brain MRI scans

William Stallcup, Ph.D., professor at Sanford Burnham Prebys Medical Discovery Institute (SBP), recently published an overview on a protein called NG2 that plays an important role in glioma. Glioma is the most common form of brain cancer, with over 20,000 new cases in the U.S. each year. More than half of all gliomas are classified as glioblastoma, for which the average survival time is only 15 months. We spoke with Stallcup about the implications of NG2 research studies.

What is NG2 and why is it important in glioma?

NG2 is a proteoglycan—a protein on the cell surface with lots of sugars attached to it. It enhances signaling that causes cells to proliferate and move around more easily—exactly what you don’t want in cancer. NG2 is a triple threat because its actions in three cell types help brain tumors grow and spread—the cancer cells themselves, and cells that form new blood vessels that supply tumors with oxygen and nutrients, and immune cells called macrophages, which gliomas convert into their support system. We’ve shown that removing NG2 from any of these cell types slows down glioma growth in mice by 60% or more.

That suggests that blocking NG2 function would be a good way to treat glioma. Is it a good therapeutic target?

To answer that, I should first explain the challenges of treating brain cancer. Not all kinds of drugs can get into the brain, but small molecules can, and those drugs usually block enzymes or receptors. Because NG2 is a different kind of protein, we’d have to think about alternative strategies, like using inhibitory RNAs to reduce production of NG2.

NG2 may also be a good prognostic indicator, since NG2 expression by glioma cells correlates with their malignancy (i.e. the more NG2, the worse the outcome for the patient). Assessing how much NG2 is made by the tumor cells might help guide decisions about how aggressive the treatment strategy should be.

Just as importantly, understanding how NG2 interacts with other proteins to promote glioma growth could point to other ways to stop these tumors from growing. And new drugs are definitely needed—most gliomas are treated with surgery and chemo, which aren’t successful in advanced cases.

What led you to study NG2 and its function in brain cancer?

I actually discovered the protein when I was a postdoc, so my lab has been studying it for the last 30-plus years. A lot of our early work showed how NG2 supports proliferation and migration of immature brain cells during development. When NG2 was found to be present at high levels in glioma, we realized that our expertise put us in a great position to advance knowledge of this often devastating cancer.