TAU research: Blocking inflammatory pathway could stop spread of cancer

‘Understanding how and why brain metastasis occurs is an urgent challenge facing cancer researchers today’

By MAAYAN JAFFE-HOFFMAN
Picture of the researchers team: (Left to right) Malak Amer, Prof. Neta Erez and Dr. Hila Doron (photo credit: TAMAR SHAMI)
Picture of the researchers team: (Left to right) Malak Amer, Prof. Neta Erez and Dr. Hila Doron
(photo credit: TAMAR SHAMI)
A team of Tel Aviv University researchers have discovered that brain metastasis is facilitated by takeover of a physiological inflammatory pathway by the brain cells that maintain a protected environment in the brain. Known as astrocytes, these brain cells 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.
“Understanding how and why brain metastasis occurs is an urgent challenge facing cancer researchers today,” said Prof. Neta Erez of the Department of Pathology at TAU’s Sackler Faculty of Medicine, the lead author of the study.
Brain metastases are among the deadliest tumor metastases, with a median survival period of less than one year, and the incidence of brain metastasis is rising, according to TAU. Blocking this pathway could prevent these metastases from developing, according to the research, which was published in Cell Reports last week.
Metastases is when cancer cells break away from the main tumor and enter the bloodstream or lymphatic system, spreading the cancerous tumors to other parts of the body.
Specifically, the scientists used a mouse model of spontaneous melanoma brain metastasis to study the interactions of melanoma tumors within the brain micro environment to make their discovery.
“We discovered that tumor cells recruit these inflammatory factors to hijack their way to the brain,” said Erez. “We identified a specific factor that mediates their attraction to the brain and showed that brain metastasizing melanoma cells express the receptor for the inflammatory factor, which is how they respond to this signal.”
Significantly, when the researchers used genetic tools to inhibit the expression of the receptor on melanoma cells, they successfully blocked the ability of tumor cells to respond to astrocyte signaling – and the development of brain metastasis was significantly inhibited.
The research was validated in the brain metastases of patients who had undergone brain surgery.
Now the researchers are investigating the trigger that instigates inflammation in the brain, which promotes metastasis.