|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
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.