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Can Targeting Brain Pathways Inhibit Brain Metastasis in Patients With Melanoma?

By: Joseph Fanelli
Posted: Friday, September 6, 2019

According to research findings presented in Cell Reports, brain metastases in patients with melanoma may be caused when tumor cells take possession of proinflammatory signaling in astrocytes, but blocking this pathway to stop the expression of this inflammatory receptor on the melanoma cells may impede tumor growth. Consequently, concluded Neta Erez, PhD, of Tel Aviv University, Israel, and colleagues, the CXCL10-CXCR3 brain axis could provide a potential target for preventing brain metastasis.

“We discovered that tumor cells recruit these inflammatory factors to hijack their way to the brain,” Dr. Erez said in a Tel Aviv University press release. “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.”

In this trial, the investigators utilized a previously established mouse model of spontaneous melanoma brain metastasis. The model, which is based on the subnormal implantation of melanoma cells, repeats the pathologic process of spontaneous metals after surgical removal of a primary tumor. The experiments were performed with primary astrocytes isolated from adult mice.

Dr. Erez and colleagues found that the chemokine CXCL10 is upregulated in metastasis-associated astrocytes in mice and humans, and it seems to play a significant role in the chemoattraction of melanoma cells. Furthermore, CXCL10’s receptor CXCR3 is also upregulated in brain-tropic melanoma cells. When the investigators targeted melanoma expression of CXCR3 with nanoparticle-mediated small-interfering RNA delivery or by short-hairpin RNA transduction, melanoma cell migration was inhibited, and brain metastasis was diminished in vivo. 

These “reciprocal interactions,” the authors noted, between melanoma cells and astrocytes play a key role in the formation of brain metastases. The researchers are currently studying the trigger that instigates inflammation in the brain, which promotes metastasis.

Disclosure: The study authors reported no conflicts of interest.



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