Cancer cells (Melanoma) reach the brain by Immune System "fraud".

Cancer cells (Melanoma) reach the brain by Immune System "fraud".
melanoma cells // Photo: Getty Images

Researchers at Tel Aviv University led by Prof. Neta Erez, and Dr. Hila Doron and research student Malak Amer, found that metastases of violent skin cancer (melanoma) reach the brain by immune system "fraud".

They "impersonate" the cells of the immune system itself, which are recruited to combat simulated tissue damage in the brain. 

The researchers have developed a method to neutralize the mechanism of deception that may prevent metastasis in melanoma patients in the future. 

The research (link to the study), was carried out in collaboration with Prof. Ronit Satchi-Fainaro, head of the Cancer and Nanotechnology Research Laboratory, at Tel Aviv University.

"Melanoma skin cancer is known to be a violent and deadly disease, mainly because it sends metastases to vital organs in the body, and in many cases to the brain," says Professor Erez. 

"We wanted to find out how cancer cells reach brain defenses and penetrate them to create metastases. 

Based on previous research, we have focused on brain tissue cells called astrocytes, which are located in the blood-brain barrier, and their role is to maintain the proper structure of the brain," she notes.

"It is known that in the case of brain tissue damage, astrocytes secrete substances that signal immune cells throughout the body and call them to the brain". 

Immune cells reach the brain in a dedicated pathway that opens for them. 

We tested a possible link between this vital mechanism and the metastatic mechanism of melanoma. 

As part of this study, the researchers examined melanoma mice model, as well as tissues of human brain melanoma, which were removed by surgery in an effort to save patients' lives. 

It was found that in some melanoma cells, a receptor activated by the inflammatory receptor CXCL10 is exactly the same as the receptor in the inflammatory cells of the immune system.

This is how they "deceive" the immune system, and use the proper pathway to reach the brain and penetrate it.

"After discovering the mechanism, we wanted to find out if there was a way to block it,"says Professor Erez. 

"Using genetic methods, we neutralized the receptor for CXCL10,  so that cancer cells could not respond to the astrocytes reading." 

The results were promising: in mice in which the receptor was neutralized much less metastatic brain development.

Inflammatory Activation of Astrocytes Facilitates Melanoma Brain Tropism via the CXCL10-CXCR3 Signaling Axis
  • Hila Doron 
  • Malak Amer
  • Nour Ershaid
  • Ronit Satchi-Fainaro
  • Tobias Pukrop
  • Neta Erez