Israeli Scientists Find Way to Prevent Melanoma Metastasis to the Brain

A group of researchers from the medical school at Tel Aviv University discovered the mechanism by which melanoma cells—the most dangerous type of skin cancer—penetrate the brain, forming metastases there. In experiments on mice, they managed to block this mechanism, halting the process of cancer spread to the brain. This discovery could be an important step towards overcoming this deadly disease.

Melanoma is the deadliest form of skin cancer. Its insidiousness lies in its ability to grow actively and metastasize to the brain. Such metastases are virtually untreatable, making the prognosis for people with advanced melanoma extremely unfavorable. The average survival in such cases rarely exceeds six months.

“A few years ago, patients with advanced melanoma died from metastases in other parts of the body—the tumor foci in the brain simply did not have time to form in sufficient volume to cause death,” explains the lead author of the study. “But the possibilities of oncology are constantly expanding; thanks to new treatment methods, patients with melanoma live longer, which is why doctors are increasingly diagnosing brain metastases. In such conditions, one of the primary tasks facing cancer researchers is to understand the mechanism of melanoma spread to the brain.”

To address this task, Israeli specialists conducted an experiment involving laboratory rodents infected with melanoma. After waiting for the cancer cells to spread into the brain tissue, they began to study the characteristics of their interaction. As a result, the researchers found that melanoma cells enter the brain by deception. The main barrier for them is the blood-brain barrier. This is a kind of filter that prevents dangerous microorganisms and substances circulating in the blood from penetrating the central nervous system.

However, this barrier has gates through which nutrients enter the brain from the arterial bloodstream. Special cells—astrocytes—guard these gates, and their role is to protect the brain and maintain its functions. When they detect any damage to brain tissue, they begin to actively release inflammatory factors, attracting immune cells.

The protein CXCL10 serves as one of these factors, with receptors for it present on the membranes of immune system cells. By binding to it, they receive a signal to urgently move toward the brain. When they reach their destination, astrocytes open the gates of the blood-brain barrier for them.

A Wolf in Sheep's Clothing

The researchers at Tel Aviv University found that melanoma cells use the same mechanism. They convince astrocytes of the presence of an inflammatory process in the brain tissue, causing them to send the corresponding signal to the immune system. The “gate” of the protective barrier opens, but instead of immune cells, a stream of melanoma cells is directed there. The latter, as the researchers established, just like the body's protective cells, have receptors for the protein CXCL10 on their surface, allowing them to easily disguise themselves as such, opening a path to the brain.

“The blood-brain barrier is not actually impenetrable,” explains one of the authors of the study. “Its gates open when presented with a special pass. One could say that by pretending to be immune cells, melanoma uses someone else's pass, deceiving its way into the brain.” The researchers also found that skin cancer cells begin to interact with astrocytes even at the early stages of the disease, before it spreads throughout the body.

On the Threshold of New Treatment

Understanding the mechanism gives researchers the ability to control it. Thus, having learned the way melanoma cells use to penetrate the brain, they conducted another experiment. Using genetic engineering, they suppressed the production of the receptor for the protein CXCL10 present on the membrane surface of cancer cells, thereby depriving them of the ability to capture signals from astrocytes and respond to them.

As a result, in mice that were implanted with the modified melanoma cells with the inhibited receptor, the number of metastases in the brain was almost half compared to their counterparts that were transplanted with ordinary, unmodified cancer cells. “The process of metastasis to the brain has significantly slowed down,” noted the Israeli scientists.

After the study on rodents, the authors repeated it on humans. They studied the same processes on samples of tumor tissue removed from the brains of patients with advanced melanoma. It turned out that in humans, astrocytes produce the same inflammatory factors, and tumor cells have identical receptors for them. “This means that the discovered link between the protein CXCL10 and its receptor can serve as a potential therapeutic target for preventing the metastasis of melanoma tumors from the skin to the brain,” the scientists assert.