Cancer Stem Cells Spur Glioma Angiogenesis, Could Hold Key to Brain Tumour Therapy

Stem cell-like glioma cancer cells that share many characteristics with normal stem cells propel the lethal growth of brain cancers by promoting tumour blood vessel formation, and may hold the key to treating these deadly cancers, a research team reported in the August 15th issue of Cancer Research.

Led by Jeremy Rich, M.D., associate professor at the Preston Robert Tisch Brain Tumour Centre 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 tumours.Gliomas are the most common type of brain tumour, making up about half of all diagnosed primary (or non-metastatic) brain tumours. About 17,000 people in the United States are diagnosed with a primary brain tumour 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 tumour growth so that gliomas can be targeted with new drugs. “Malignant brain tumours are highly lethal, despite aggressive surgery, radiation, and chemotherapy,” said Dr. Rich. “We believe targeting the cancer stem cells of brain tumours may offer a novel therapy that will help to decrease the blood supply feeding a growing tumour, and therefore decrease or stop that tumour’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 tumours 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 tumours 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 tumour 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 tumours 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 tumour 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 tumour 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 tumour 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.(Source: Cancer Research: American Association for Cancer Research: August 2006).