A team led by Michelle Monje of the Ludwig Center at Stanford has discovered that brain tumors known as high-grade gliomas form synapses—or connections with neurons—and tap electrical signals from healthy neurons to drive their own growth. Reported in September in Nature, the study further revealed that many of the cancer cells within the brain tumors also contain cell-to-cell electrical connections known as gap junctions, which help transmit and amplify impulses. High-grade gliomas include glioblastoma, the most common adult brain tumor, and the highly aggressive pediatric malignancy, diffuse intrinsic pontine glioma (DIPG), among others. Michelle and her team showed that 5-10% of glioma cells within each tumor receive synaptic signals, and about 40% exhibit prolonged potassium-evoked currents that are amplified via gap junctions. Boosting electrical signals into tumors accelerated their growth. The researchers also noticed that healthy neurons near tumors tend to be hyperexcitable, which could explain why many HGG patients suffer seizures. Experiments demonstrated that interrupting these signals with an existing anti-epilepsy drug greatly reduced the growth of human gliomas in mice. The team is investigating whether blocking electrical signaling within tumors could help people with HGGs.
This article appeared in the April 2020 issue of Ludwig Link. Click here to download a PDF (1 MB).