Effect of Ion Transporters in Brain Tumor Stem Cell Migration

Dr. Quinones-Hinojosa's laboratory and others have discovered that the protein ion cotransporter NKCC1 may hold clues to how glioblastoma invades the normal brain. The lab is studying how this protein maneuvers the cell and working to pinpoint new molecular targets for targeted cancer therapy.

The team has previously found that cells with an over-expression of NKCC1 appear to move farther and faster than regular cells in validated experiments. The electroneutral NKCC1 protein allows the cell to grip more tightly to adjacent tissue, allowing the cell to propel itself farther through the brain.

When cells underexpressed NKCC1 or were depleted of the protein, focal adhesion molecules that served as Velcro-like sources were bigger and kept the cells anchored in place, making it harder for the cells to propel through the brain and decreasing migration.

Understanding how cancer cells use NKCC1 to migrate and invade healthy brain brings scientists closer to understanding how and where to target glioblastoma effectively. For example, bumetanide, a simple water pill routinely used to reduce swelling and fluid retention caused by various medical problems, blocks NKCC1. The lab found that when bumetanide was added to human tumor cells, it blocked the NKCC1 channel and slowed the pace of cell movement both in the petri dish and in mice with cancer. These findings allow for the potential use of bumetanide in a human clinical setting.

Project team

Lab members studying the effect of the NKCC1 ion cotransporter in brain tumor stem cell migration include:

• Paula Valentina (Paula) Schiapparelli, Ph.D.
• Paola Suarez Meade, M.D.