Blocking Inflammatory Pathway May Stop Brain Metastasis from Melanoma

Melanoma brain metastasis occurs when tumor cells hijack an inflammatory pathway in the brain and blocking this pathway could prevent metastasis from developing, according to a new study by Tel Aviv University.

According to the American Association of Neurological Surgeons, metastatic brain tumors occur when tumors spread to the brain from a primary neoplasm located in another part of the body.² Historically, patients were more likely to die from a metastatic tumor on another part of the body before a metastatic brain tumor was evident. However, since cancer treatments are improving and patients are living longer, there is a greater incidence of diagnosed brain metastasis.

The study, published in Cell Reports, focused on melanoma brain metastasis, because melanoma has one of the highest rates of mortality and metastasis, occurring frequently in the brain, according to the researchers.

Using a melanoma brain metastasis model, researchers examined the interactions between melanoma tumors with the brain microenvironment and discovered that the metastasis is facilitated by the takeover of a physiological inflammatory pathway by astrocytes, the brain cells that maintain a protected environment in the brain. Additionally, astrocytes respond to tissue damage in the brain by instigating an inflammatory and tissue repair response to contain the damage, secreting inflammatory factors that recruit immune cells.

The researchers found that tumor cells use these inflammatory factors to hijack their way into the brain and that brain-metastasizing melanoma cells express the receptor for the inflammatory factor, allowing them to respond to the signal.

Significantly, when the researchers used genetic tools to inhibit the expression of the receptor on melanoma cells, it successfully blocked the ability of tumor cells to respond to astrocyte signaling and the development of brain metastases was significantly inhibited.

The findings suggest that blocking a signaling pathway that includes the inflammatory factor known as CXCL10-CXCR3 may prevent brain metastasis, according to the study authors.

The researchers are currently investigating the trigger that instigates inflammation in the brain that promotes metastasis.

Reference

• Blocking Inflammatory Pathway Key to Preventing Brain Metastasis from Melanoma [press release]. Tel Aviv University website. Published August 19, 2019. https://www.aftau.org/weblog-medicine--health?&storyid4704=2475&ncs4704=3. Accessed September 4, 2019.
• Metastatic Brain Tumors. American Association of Neurological Surgeons website. https://www.aans.org/en/Patients/Neurosurgical-Conditions-and-Treatments/Metastatic-Brain-Tumors. Accessed September 4, 2019.