Researchers at Tel Aviv University believe they have found a “pathway” that causes melanoma cells to spread to the brain, and may have found a way to block this from happening.
The study was conducted on mice, but has also been validated on samples of human brain tissue where melanoma had spread, the researchers said.
“Melanoma is the deadliest skin cancer due to its high rate of metastasis, frequently to the brain,” said Prof. Neta Erez of the Department of Pathology at TAU’s Sackler Faculty of Medicine, the lead author of the study.
“The prognosis of patients with brain metastases is very grim,” Erez said.
Patients used to die from metastases in other parts of the body, before they were spotted in the brain. However, because treatments have improved and patients are living longer, “the incidence of diagnosed brain metastases is increasing. Understanding how and why brain metastasis occurs is an urgent challenge facing cancer researchers today,” Erez said.
The researchers set out to find out how these cells spread to the brain and how this transmission could be halted. In their work, they took mice with spontaneous melanoma brain metastasis and studied how it reacted with the brain.
Astrocytes are among the most abundant cells in the brain tissue. Their role is to protect the brain and maintain its function through tissue repair. If astrocyte cells sense tissue damage, such as a stroke, they set off an alarm and start secreting inflammatory factors that attract immune cells to the brain.
“We discovered that these melanoma cells can activate these inflammatory pathways that lead to the brain, and then hijack this pathway,” said Erez in a phone interview. “They trigger the inflammatory secretions, and then take advantage of this pathway which helps them enter the brain.”
When the researchers used genetic manipulation to neutralize the receptors in the melanoma cells, they successfully blocked the ability of the tumor cells to respond to the astrocyte signaling. “The development of brain metastases was significantly inhibited,” the university said in a statement.
The research, emphasized Erez, was done on mice and not humans. But the researchers validated their results in the brain metastases of patients who had undergone brain surgery. They found that in humans, the astrocytes cells express the same inflammatory factor — called CXCL10 — and that the human tumor cells also express the same receptor, CXCR3, as did the mice.
“This suggests that the identical mechanism is operative in humans,” the statement said.
“Our findings suggest that blocking this signaling pathway may prevent brain metastasis,” Erez said. “The CXCL10-CXCR3 axis may be a potential therapeutic target for prevention of melanoma brain metastasis.”
The researchers are now studying what could be the trigger that instigates inflammation in the brain, which promotes metastasis.
The research, published in Cell Reports on August 13, was conducted by TAU graduate students Dr. Hila Doron and Malak Amer, in collaboration with Prof. Ronit Satchi-Fainaro, also of TAU’s Sackler Faculty of Medicine.
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