Metastases slowed down
Israeli scientists have slowed down the metastasis of melanoma in the brain by 60-80%
Tatiana Matveeva, "Scientific Russia"
Researchers from Tel Aviv University for the first time deciphered the mechanism that allows skin cancer to form metastases in the brain, and managed to delay the spread of metastases by 60-80% with the help of existing treatment methods, reports EurekAlert!. The results of the work are published in the scientific journal JCI Insight (Pozzi et al., MCP-1/CCR2 axis inhibition sensitizes the brain microenvironment against melanoma brain metastasis progression).
"At a late stage, 90% of patients with melanoma (skin cancer) develop brain metastases,— explains Professor Ronit Satchi-Fainaro. — This is a mysterious statistic. We usually expect that metastases can form in the lungs and liver, but the brain is considered an organ that is well protected. The blood-brain barrier keeps harmful substances from entering the brain, but it doesn't seem to work here: skin cancer cells circulate in the blood and reach the brain."
Scientists have found that in patients with melanoma with brain metastases, cancer cells interact with astrocytes — star-shaped cells that are responsible for homeostasis, that is, maintain a stable environment and conditions in the brain. Cancer cells exchange molecules with astrocytes and destroy them. In addition, cancer cells "recruit" astrocytes so that they do not interfere with the spread of metastases, creating local inflammation in the areas of interaction between melanoma cells and astrocytes, which increases the permeability of cancer cells through the blood-brain barrier, as well as their division and migration.
Astrocytes begin to secrete a protein that promotes inflammation — MCP-1 (also known as CCL2) — and in response, cancer cells begin to express their CCR2 and CCR4 receptors, which are responsible for destructive communication with astrocytes. To test this mechanism, the team suppressed the expression of the protein and its receptors in genetically modified laboratory models and in 3D models of primary melanoma and brain metastases. The researchers used both an antibody (a plasma protein) and a small molecule to block the MCP-1 protein. And with CRISPR scissors, they edited cancer cells and cut out two genes that express two corresponding receptors, CCR2 and CCR4. Using each of the methods, the scientists were able to slow down the spread of metastases.
"It is important to note that melanoma metastases in the brain are very aggressive and have a poor prognosis for 15 months after surgery, radiation and chemotherapy. We have reached a delay [in metastasis — HP.] by 60-80%, depending on the stage of intervention," the authors add. They achieved the best results in treatment immediately after surgery, when the patient had primary melanoma removed. So scientists were able to prevent the penetration of metastases into the brain. Both the antibody and the small molecule they used have already been tested in the treatment of other human diseases, so they can simply be repurposed to fight melanoma.
Portal "Eternal youth" http://vechnayamolodost.ru