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Monday, May 15, 2006
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Researchers Find that Tumor Stem Cells are Good Models for Brain Tumor Research

Researchers at the National Cancer Institute (NCI) and the National Institute of Neurological Disorders and Stroke (NINDS), both part of the National Institutes of Health, have found that tumor stem cell lines derived directly from human glioblastoma brain tumors are a better model to study the biology and physiology of glioblastomas than are cancer cell lines that have been commonly used in cancer research laboratories. They also discovered the conditions under which to preserve the biological integrity and genetic characteristics of these glioblastoma tumor stem cell lines. The study results appear in the May 15, 2006, issue of Cancer Cell*.

Cells in traditional cancer cell lines often bear little resemblance to the cells found in the corresponding original tumor. Glioblastoma tumor stem cells, however, accurately reflect the biological mechanisms and genetic characteristics of the parent tumor. These tumor stem cells are capable of self-renewal — a characteristic that is essential for tumor growth — and of developing into glioblastomas when injected into mice with compromised immune systems. Thus, these tumor stem cell lines offer a powerful new tool to study the biology of glioblastomas and to test drugs for treatment of this disease.

"This study illustrates that traditional cancer cell lines are a flawed model and poorly represent human tumors," said Howard Fine, M.D., study leader and chief, Neuro-Oncology Branch in NCI's Center for Cancer Research. "We may be making inexact or possibly wrong conclusions about the biology of these tumors and could be utilizing inappropriate models to screen therapeutics. This is one of the first studies to conduct an in-depth characterization of the biology of glioblastoma tumor stem cells, and we have shown that these tumor stem cell lines may ultimately offer a model system that more accurately represents the biology of the tumors actually found in patients."

Traditional cancer cell lines are created by growing cancer cells in a culture dish. Cultured cells allow investigators to study the physiology of tumor cells outside a living organism and are grown in solutions that contain blood serum, which provides nourishment for the cells. Normal brain (neural) stem cells, however, cannot be grown in solutions containing serum because it causes the cells to differentiate, mature and stop growing.

In this study, glioblastoma tumor stem cell lines were grown in two different culture conditions, one containing serum and another that was serum-free. The biology and genetic characteristics of the resulting glioblastoma stem cell lines were then compared with those of traditional glioblastoma cell lines — grown with serum — and normal neural stem cell lines — grown in serum-free solutions. Investigators wanted to identify which cell line most closely matched the biological characteristics of the glioblastoma cells isolated from fresh brain tumors.

This study showed that the glioblastoma stem cells grown under the two different conditions, serum or serum-free, had vastly different physiological and genetic characteristics. The glioblastoma tumor stem cells grown under serum-free conditions had the same characteristics as the parent glioblastoma cells. The glioblastoma tumor stem cells cultured with serum, however, lost all biological and genetic characteristics of the original tumor cells and ultimately assumed the characteristics of the traditional glioblastoma cell lines that have been grown in serum and studied for more than 20 years.

"When serum is added to tumor stem cells, it causes them to differentiate, and they become different cells," said Fine. "For decades, we have, in a sense, been weeding out these tumor stem cells — which we have shown to be important models to understand cancer biology — with our use of traditional growth methods."

Glioblastoma multiforme is a type of glioma and gliomas are the most common primary malignant tumors of the central nervous system in adults, and primary brain tumors are now the leading cause of cancer-related deaths in children. An estimated 18,820 new cases of brain cancer will be diagnosed in the United States in 2006, and more than 12,000 will die from the disease.

The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.


*Lee J, Kotliarova S, Kotliarov Y, Li A, Su Q, Donin NM, Pastorino S, Purow BW, Christopher N, Zhang W, Park JK, Fine HA. Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines. Cancer Cell. May 15, 2006, Vol.9, Issue 5.
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