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Some Immature Brain Cells May Promote Tumors

But animal studies show cancer gene can be turned on and off

MONDAY, Jan. 7 (HealthDay News) -- Much like a child who becomes a bully while his peers are becoming thoughtful and kind, some immature brain cells go through an alteration in their development that allows them to grow into cancerous tissue, a new study finds.

National Cancer Institute (NCI) researchers have identified a chemical process that turns off the gene that prevents the growth of tumor tissue. The gene can be turned back on and the risk of tumor tissue reduced, said the team, which suggests a potential avenue for future cancer treatment research.

The cells in question are known as tumor-initiating cells with stem-like properties (TICs). These cells are thought to cause the aggressive brain cancer, glioblastoma multiforme, when there is a breakdown in the way in which the cells' genes are expressed. TICs behave like stem cells in many ways, but, instead of growing into healthy tissues, they grow into a tumor. Researchers have reported the presence of TICs in breast, colon, lung and brain cancers.

The NCI team used tumor tissue from people with glioblastoma multiforme to develop a cell that ignored the effects of two proteins -- bone morphogenetic protein-2 (BMP2) and ciliary neurotrophic factor (CNTF) -- that usually cause brain stem cells to grow. Instead, the cells partially responded to one protein (BMP2) and not the other, which the researchers explained as an immature, developing cell response.

When the researchers compared the behavior of the specially grown cells with normal neuronal stem cells, they learned that one of the genes that regulates the response to BMP2 was not working in the new cells. When they turned that gene on, the cells began to respond more normally and were less likely to grow into tumor tissue. Further study revealed that the gene was blocked by a chemical process called methylation, which is thought to be responsible for silencing genes that would otherwise prevent many other cancers.

Methylation, the chemical process that could be behind allowing cancer growth, is also key to the growth of cells in young brains, said the researchers, who found that demethylating the newly created cells caused them to behave more normally and in a similar way to brain cells in embryos, confirming the researchers' suspicion that immature brain cells may be at the root of cancer growth.

The team then analyzed 54 glioblastoma multiforme tumors and found that one in five (20 percent) contained signs of the same difficulty with the BMP2 gene that the researchers saw in the lab. These tumors were also methylated.

"This research highlights an example of a stem cell whose normal development has been blocked in such a way as to prevent it from differentiating as well as to force it to contribute to the development of an aggressive tumor," research leader Dr. Howard Fine, chief of the Neuro-Oncology Branch at the NCI's Center for Cancer Research, said in a prepared statement. "The results we have generated can help us better understand the biology of neuronal stem-like starter cells in glioblastoma multiforme and other cancers, and give us a strong rationale for investigating BMPR1B as a potential target for therapeutic development."

The study was published in the January issue of Cancer Cell.

More information

To learn more about brain and spinal cord cancers visit the American Cancer Society.

-- Madeline Vann

SOURCE: National Cancer Institute, news release, Jan. 7, 2008

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