Breakthrough in slowing the spread of deadly brain cancer

The diagnosis of a gioblastoma, one of the most common and deadliest of brain tumors, can be devastating.  While the cancer alone is harmful, its most lethal aspect is the speed at which it travels through the brain, infecting healthy tissue.

Trying to control the cancer’s spread has been one of the biggest hurdles in treating these kinds of brain cancers.  But now, researchers from John Hopkins University in Baltimore, Md., have potentially revealed an effective way to slow it down.

“These [cancer] cells move through the brain as if nothing matters,” said the study’s lead author Dr. Alfredo Quinones-Hinojosa, an associate professor of neurosurgery and oncology at the John Hopkins University School of Medicine.  “So we asked, what are the thing  that make them migrate? They must have something that makes them act like ‘spidermen’ – allowing them to move quickly and stick to things along the way.”

Quinones-Hinojosa and his team focused on a protein called NKCC1, which is used by all kinds of cells to migrate.  The protein helps transport sodium, potassium and chloride to tumor cells, allowing them to more easily regulate their volume.

“Cells have to figure out how to move through a lot of stuff, so they have to regulate that ability to move their bodies,” said Quinones-Hinojosa.  “The cells can get a little but plump or skinny, depending on where they need to fit.  Just think about how a worm moves. It contracts its back to move forward, then it will stretch itself out.  For the cell to be able to move, it has to regulate its body shape in a similar way.”

The research team found the cancer cells with more NKCC1 moved farther faster because of this ability to manipulate their shapes and propel themselves through tissue.  They also discovered that when NKCC1 was absent, the cancer cells had to compensate by growing larger food processors.  These processors have a Velcro-like quality to them, so when they grow large, they act like an anchor that keeps the cell in place.  Smaller food processors allow for more mobility.

“It reminds me of the recent Mission Impossible movie,” said Quinones-Hinojosa.  “Tom Cruise’s gloves are like the little food processors, allowing him to stick to the building and move forward.  When his gloves turn red, they don’t stick to the window of the building anymore.  Imagine when you take the protein away, the cancer cells turn red.”

To better understand the role of NKCC1 in cancer mobility, the researchers tried blocking the protein with the diuretic bumetanide, a water pill typically used to reduce swelling and fluid retention.  When they added bumetanide to tumor cells in the lab or in human cancer cells in mice,

“This is a drug that is approved for cardiac disease, but what it tells us is that there are drugs already out there that can affect this type of little protein,” said Quinones-Hinojosa.  “So if we can learn more about [the protein] and find better drugs that works similar to this drug, we can possibly affect the survival of patients.”

According to the American Brain Tumor Association, gioblastomas represent about 17 percent of primary brain tumors and are considered highly malignant.  After the diagnosis of this kind of tumor, the median survival for patients is only 14.6 months, making surgical options and radiation treatments nearly impossible.

Because of this bleak prognosis, Quinones-Hinojosa is ready to expand on this research to find better drugs that can block the NKCC1 protein and potentially develop a drug that can slow the spread of cancer cells.

“If we can change the progression of the disease, maybe we can help them survive years, if not longer,” said Quinones-Hinojosa.  “This brain tumor dispersal is really what is taking their lives.”