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NIH researchers identify key factor that stimulates brain cancer cells to spread
Date:8/18/2009

ell adhesion is important for development, and that there are many parallels between what happens during development and what happens in cancer," says Dr. Brady-Kalnay. For instance, she notes there is some evidence that cancer cells have turned back the developmental clock and reverted to an embryonic stem cell-like state.

In their new study published in Cancer Research, Dr. Brady-Kalnay and her team report that in GBM cancer cells, the PTPmu protein is cut into fragments, a process known as proteolysis. One might expect that the loss of intact PTPmu would simply cause the cells to detach from their surroundings. However, the fragments also appear to act as signals that stimulate the cells to move and to thrive outside of their normal surroundings.

The researchers found the PTPmu fragments in GBM tumors that had been surgically removed from patients and in GBM cells grown in the laboratory. Next, they examined how these fragments affected the migration of GBM cells in a petri dish. They observed that adding more of the intact protein to the cells or treating the cells with a chemical inhibitor of proteolysis reduced the cells' ability to migrate.

Finally, they showed that it is possible to suppress the effect of the fragments, even without restoring the intact PTPmu protein. This last experiment built upon a collaboration between Dr. Brady-Kalnay and Frank Longo, M.D., chair of the neurology department at Stanford University School of Medicine. The two researchers had previously designed a very small protein, or peptide, capable of attaching to PTPmu and blocking its effects on retinal cell migration. Here, Dr. Brady-Kalnay and her team tested this peptide in GBM cells, and found that it blocked their ability to migrate, too.

The peptide cannot currently be used to treat GBM, because it would be broken down rapidly if it was injected directly into the body. The researchers hope to develop injectable compounds that mimic the pepti
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Contact: Daniel Stimson
nindspressteam@ninds.nih.gov
301-496-5751
NIH/National Institute of Neurological Disorders and Stroke
Source:Eurekalert

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