Protein propels cancer through brain

JOHNS HOPKINS (US) — A protein that moves chemicals in and out of cells also appears to be critical to the rapid progression of the deadliest, most common form of brain cancer.

The findings, reported in the journal PLoS Biology, also suggest that an inexpensive FDA-approved drug already on the market could slow movement of cancerous glioblastoma cells and contain their spread.

“The biggest challenge in brain cancer is the migration of cancer cells. We can’t control it,” says study leader Alfredo Quinones-Hinojosa, associate professor of neurosurgery and oncology at the Johns Hopkins University School of Medicine.


“If we could catch these cells before they take off into other parts of the brain, we could make malignant tumors more manageable, and improve life expectancy and quality of life. This discovery gives us hope and brings us closer to a cure.”

Glioblastoma, diagnosed in roughly 10,000 Americans each year, is so aggressive that the average life expectancy after diagnosis is just 15 months, Quinones says. The cancer invades healthy brain tissue so quickly and completely that surgical cures are virtually impossible. Advances in radiation and chemotherapy have been slow in coming.

In a search for ways to prevent or limit glioblastoma spread, researchers worked with human tumor cells in the laboratory and with tumor cells injected into mice. They focused on a protein called NKCC1, which transports sodium, potassium, and chloride ions into and out of cells and regulates cell volume.

Quinones-Hinojosa and his team found that tumor cells with more NKCC1 move farther, apparently because the protein make it easier for tumor cells to grab onto other cells and propel themselves through the brain.

The more NKCC1 they contain, the scientists discovered, the faster the glioblastoma cells can travel. When NKCC1 was absent, the cells had larger focal adhesions, which allow for Velcro-like attachment to surrounding cells. Larger adhesions, Quinones-Hinojosa says, appear to keep the cells more anchored in place, while smaller ones made cells more mobile and allowed for more migration.

The team was able to block NKCC1 with the diuretic bumetanide, a simple water pill routinely used to reduce swelling and fluid retention caused by various medical problems. Added to tumor cells in the laboratory and in mice, the drug slowed the pace of cell movement.

Less invasive cells, Quinones-Hinojosa notes, would keep tumors more localized and make them easier to remove surgically. The researchers were also able to correlate human tumor grade with levels of NKCC1. Less aggressive tumors, they discovered, had smaller amounts of the protein, while more aggressive tumors had more.

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