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Cancer cells can "disturb" the nerves of the brain



  Nerve and glial cells, micrograph with fluorescent light.

Neurons (blue) play a surprising role in the development of some cancers in the brain. Daniel Schroen / Cell Applications INC / Science Photo Library

Tumor cells can implant and feed on the complex neural network of the brain, according to a trio of studies. This shameful ability could explain the mysterious behavior of certain tumors and suggest new ways to treat cancer.

The studies 1

2 3 published on September 18 in Nature describe this amazing ability in brain tumors called gliomas, as well as in some breast cancers that spread to the brain. The findings confirm the increasing recognition of physicians and scientists that the nervous system plays an important role in the growth of cancer, says Michelle Monje, pediatric neurooncologist at Stanford University in California and lead author of one of the studies 1 .

Still, finding cancer cells that behave like neurons was a surprise. "It's disturbing," says Monje. "We do not think that cancer forms an electrically active tissue like the brain."

Feeding the brain

Frank Winkler, neurologist at the University of Heidelberg and principal author of another of Nature studies 2 came across this phenomenon in 2014 when investigating communication networks built by cells in some brain tumors. He and his team discovered in the tumors synapses, structures through which neurons communicate with each other. It was "crazy stuff," says Winkler. "Our first reaction was: & # 39; That's hard to believe. & # 39;

The researchers estimated that the tumor synapses would occur by chance. However, as reported by Winkler and his colleagues in their latest study, they found synapses in glioma samples of cultured cancer cells, human glioma tumors transplanted into mice, and glioma samples from ten individuals.

At the same time, Winkler's team Monje and her colleagues studied adult glioma synapses and independently discovered synapses between neurons and cells in pediatric gliomas. The separate but parallel research of the Monje and Winkler teams also showed that the tumor synapses promote the growth of cancer cells. The teams independently reported on their findings in two of the recent studies.

Monje's findings explain some of the enigmatic features of glioma she sees in her patients. The tumors are known to be difficult to treat: instead of forming a hard, compact mass, they weave through the brain and are difficult to remove. When a glioma infiltrates a large part of the brain, patients usually have few symptoms because the tumor does not seem to disturb many brain circuits, Monje says. "And that makes sense now, because it depends on its function."

"If this is generally true for more cancers, it is not necessarily surprising why it was so difficult to treat cancers in the brain," says Johanna Joyce, a cancer biologist at the Ludwig Institute for Cancer Research, University of Lausanne, Switzerland. The tumor cells are essentially integrated into the neuronal network of the brain. "It's sobering."

Deadly integration

The phenomenon is not limited to brain tumors. In a third article 3 published on September 18, Douglas Hanahan, cancer researcher at the Swiss Institute for Experimental Cancer Research in Lausanne, and his team describe breast cancer cells in the brain that act like neurons. The researchers discovered this ability when they searched gene expression data in tumors. Fatal breast cancers, called triple negative tumors, set up genes involved in signaling between neurons. These types of breast cancer are known to spread to the brain and are difficult to treat there.

Hanahan and his colleagues showed that breast cancer cells form a special type of synapse when they infiltrate the brain, allowing them to take on a chemical called glutamate. It is the most abundant neurotransmitter in the brain and can also stimulate tumor growth.

All three studies underline the resilience of cancer cells, says Lisa Sevenich, who studies brain cancer at the University of Frankfurt, Germany. The brain is an extremely hostile environment for cancer cells, she says. "But somehow the tumor cells manage to actually adopt and co-opt the machinery there."

The researchers hope that these results will lead to new ways of cancer treatment. In two of the most recent studies, the Winkler and Monje teams describe experiments that show that an epileptic drug slows down the spread of glioma in mice. Scientists have not yet determined whether the treatment works in humans, but they hope that disrupting the connection between tumor cells and neurons could inhibit the growth of the cancer.

The trick in developing such a treatment is to target all hybrids of neuronal cancer cells without damaging the normal connections between brain cells, says Sevenich. "Honestly, I think it's going to be very difficult," she says. "When these cells take over certain circuits that already exist in the brain, it will be difficult to be selective. But I keep my fingers crossed. "


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