Researchers at the Stanford University School of Medicine have shown for the first time that acute brain cancers incorporate into the brain’s wiring.
The tumors, called high-grade gliomas, type synapses that soothes electric signals from healthy nerve cells To drive their development.
A paper describing the findings will be published online Sept. 18 in Nature.
The discovery helps explain why gliomas are so intractable, she added.
This is such a massive type of tumors. They are actually integrating to the brain.
The study’s lead author is postdoctoral scholar Humsa Venkatesh, Ph.D..
Discovering that tumors wire themselves into the brain was unsettling Monje said. Still, she said she is optimistic about what the knowledge means for glioma patients.
Several drugs already exist for treating electrical-signaling disorders such as epilepsy, and these may prove useful for gliomas, she said.
There is actual hopefulness for this discovery, she said. We’ve been overlooking this whole facet of the disease. Today we’ve got a completely different avenue to research, one which may complement existing therapeutic approaches.
How the tumors grow
High-grade gliomas form synapses with healthy neurons that transmit electrical signals to the cancerous tissue, the study found. The tumors also contain cell-to-cell electrical connections known as gap junctions. Together, the two types of connections allow electrical signals from healthy nerve cells to be conducted into and amplified within the tumors.
High-grade gliomas include glioblastoma, a brain tumor seen in adults that has a five-year survival rate of 5%; diffuse intrinsic pontine glioma, a pediatric brain tumor with a five-year survival rate below 1%; and other diagnoses such as pediatric glioblastoma and diffuse midline gliomas occurring in the spinal cord and thalamus.
The cancer cells strongly increased the expression of genes involved in forming synapses.
The researchers then used electron microscopy, a technique that can reveal tiny details of cell anatomy, to show that structures that look like synapses exist between neurons and glioma cells.
To confirm that these synapses indeed connect healthy neurons and malignant glioma cells, the scientists studied mice with cells from human gliomas implanted in their brains.
We saw quite clear neuron-to-glioma synaptic structures Monje said.
Using brain tissue from mice with human gliomas, the researchers measured the transmission of electrical signals into and through the tumors.
And sustained electrical signals lasting one to two seconds that reflect electrical current propagated by a flux of potassium ions across the tumor cells’ membranes.
The scientists conducted experiments with a dye Drugs, and also the cells capable of blocking gap junctions to affirm that this kind of intersection originated between the tumor cells and mediated their coupling.
It was startling to see that in cancer tissue.
The researchers showed that roughly 5-10percent of glioma cells receive Synaptic signals, and about 40% exhibit potassium cells which are amplified by gap interconnections such that half of tumor cells have some type of electrical response to signals from neurons that are healthy.
Possible drug therapies
Measured before operation to eliminate glioblastoma tumors, and near the tumors, the investigators found hyper-excitability of neurons in mice with gliomas , a finding that could help explain why human glioma sufferers are prone to seizures.
Using cytogenetic Methods, which depended upon laser light
The cancer cells from mice implanted with human gliomas, the investigators demonstrated that increasing signals caused tumor growth.
Present drugs that block currents decreased expansion of High-grade gliomas found.
Meclofenamate, a drug that blocks the action of gap junctions, led to a similar drop in tumor proliferation.
Monje’s team plans to continue investigating whether obstructing electrical signaling inside tumors could help people with high quality gliomas.