Cancer Stem Cells Spur Glioma Angiogenesis, Could Hold Key To Brain Tumor Therapy

Led by Jeremy Rich, M.D., associate professor at the Preston Robert Tisch Brain Tumor Center at Duke University, the researchers found that a small subset of glioma cells expressed higher levels of a growth factor associated with cancer cell growth. They believe this subset could be a target for new therapies against these intractable brain tumors.

Gliomas are the most common type of brain tumor, making up about half of all diagnosed primary (or non-metastatic) brain tumors. About 17,000 people in the United States are diagnosed with a primary brain tumor each year. Patients with the most aggressive glioma, called glioblastoma, have an average life expectancy of less than one year despite advances in cancer treatment. To better treat cancer patients, laboratories like those of Rich are trying to better understand the causes of tumor growth so that gliomas can be targeted with new drugs.

"Malignant brain tumors are highly lethal, despite aggressive surgery, radiation, and chemotherapy," said Dr. Rich. "We believe targeting the cancer stem cells of brain tumors may offer a novel therapy that will help to decrease the blood supply feeding a growing tumor, and therefore decrease or stop that tumor's growth."

Researchers from other laboratories recently determined that a small fraction of all the cells in a glioma have special characteristics similar to brain stem cells. These stem cell-like glioma cells form tumors when implanted in animals. As the ability to form new blood vessels (called angiogenesis) to supply blood carrying nutrients is critical in cancer growth, Dr. Rich's team studied if the formation of tumors by stem cell-like glioma cells could be due to increased angiogenesis. Angiogenesis is often stimulated by a key growth factor called VEGF. Rich and colleagues found that stem cell-like glioma cells enhanced the angiogenesis of gliomas through increased levels of VEGF.

Using an antibody to mark the cancer stem cells in gliomas obtained from patient specimens, the Rich laboratory determined that between three-to-five percent of tumor cells were of the stem cell-like variety. They found that these stem cell-like glioma cancer cells expressed much higher levels of VEGF and formed more tumors with more blood vessels than glioma cells that did not have stem cell characteristics. Adding an antibody (bevacizumab, also known by the trade name Avastin) that blocks VEGF activity blocked new blood vessel formation and prevented tumor growth. The researchers suggest that the stem cell-like glioma cells, because of their support of angiogenesis, could hold an important target to suppressing the growth of brain cancer.

"VEGF antibodies may be effective as cancer therapies when combined with chemotherapy by improving delivery directly and specifically to stem cell-like tumor cells," said Dr. Rich. "Targeting VEGF in this way would not kill cancer cells directly, but instead would block the actions of adjacent cells that support the growth of their blood supply."

Dr. Rich's lab studies the complex relationships between cell signaling pathways and the development of cancer, especially in the nervous system. The lab is investigating a number of molecular targets that contribute to cancer growth and malignancy.

"Too often, brain tumor patients have been told there is no hope. Our overall objective is to give brain tumor patients that hope, while we do not expect to achieve instant victories in the near future," said Dr. Rich.

Dr. Rich's colleagues in the study included Shideng Bao, Qiulian Wu, Sith Sathornsumetee, Yueling Hao, Zhizhong Li, Anita Hjelmeland, Qing Shi, Roger McLendon and Darell Bigner, all of Duke University.