Scientists from Tel Aviv University have deciphered the mechanism that enables skin cancer to metastasise to the brain and were able to delay the spread of the disease by 60-80% using existing treatments.
Once melanoma, or skin cancer, spreads to the brain, it becomes extremely aggressive. Patients with this stage of cancer are given an average of 15 months to live, and that is following surgery, radiation, and chemotherapy.
The encouraging study was led by Prof Ronit Satchi-Fainaro and PhD student Sabina Pozzi of the Sackler Faculty of Medicine at Tel Aviv University. The results were published in the journal JCI Insight.
Corrupted astrocytes
“In an advanced stage, 90% of melanoma patients will develop brain metastases,” explained Prof Satchi-Fainaro. “This is a puzzling statistic. We expect to see metastases in the lungs and liver, but the brain is supposed to be a protected organ. The blood-brain barrier keeps harmful substances from entering the brain, and here it supposedly doesn’t do the job.”
The researchers found that in melanoma patients with brain metastases, the cancer cells ‘recruit’ cells called ‘astrocytes’, star-shaped cells found in the spinal cord and brain which are responsible for maintaining homeostasis in the brain.
“The astrocytes are the first to come to correct the situation in the event of a stroke or trauma, for example,” added Satchi-Fainaro, “and it is with them that the cancer cells interact, exchanging molecules and corrupting them.
“The astrocytes begin to secrete a protein that promotes inflammation called MCP-1, and in response to this, the cancer cells begin to express its receptors CCR2 and CCR4, which we suspected to be responsible for the destructive communication with the astrocytes.”
Spread of metastases delayed
Satchi-Fainaro and her team tried to inhibit the expression of the protein and its receptors in genetically engineered lab models and in 3D models of primary melanoma and brain metastases. The researchers used an antibody (biological molecule), a small molecule (synthetic), and employed CRISPR technology, a gene-editing technique, to successfully delay the spread of metastases by 60-80%.
The research was conducted in collaboration with scientists and physicians from Tel Aviv University, the US National Institutes of Health (NIH), Johns Hopkins University, and the University of Lisbon.
The study was funded by the European Research Council (ERC), the Melanoma Research Alliance (MRA), the Kahn Foundation, the Israel Cancer Research Fund (ICRF), and the Israel Science Foundation (ISF).