Innovative Human Cell Model Shows How Melanoma Thrives in the Brain

Using human cells and cutting-edge technology, the team created a three-dimensional (3D) model that accurately simulates the brain invaded by aggressive cancer. Published in Biofabrication, the study combines frontier science, advanced technology, and international collaboration - while also carrying a personal story: part of the team is formed by a couple of scientists who quite literally bring their work home.

Brain metastasis occurs when cancer cells migrate from the original tumor - in this case, the skin - to the brain. This stage of the disease is among the most challenging to treat, and it is associated with over 90% of cancer-related deaths.

"When melanoma reaches the brain, survival rates drop dramatically. Understanding how it adapts and alters brain tissue is essential for developing more effective therapies," says biomedical scientist Helena Borges, professor at UFRJ and collaborator at the D'Or Institute for Research and Education (IDOR).

A "Big Brother" for Watching Tumors in Real Time

To realistically simulate the brain's environment, the team used brain organoids created from human stem cells. These contain neurons and astrocytes, replicating real brain structures. The organoids were placed in microfluidic devices, where they interact with melanoma tumor cells inside a 3D system that mimics the human body.

What makes this model unique is the ability to observe, over time, what happens inside the "invaded mini-brain" without destroying it.

It's like setting up a cellular Big Brother. Instead of taking isolated snapshots at different stages, we can now film everything in real time, using different kinds of 'cameras': bioluminescence, fluorescence, PET scan."

Stevens Rehen, researcher at the D'Or Institute for Research and Education (IDOR), Pioneer Science, and collaborator at Promega

"One of the most striking discoveries was the tumor's metabolic behavior. The model revealed that metastatic melanoma releases glutamate in excess - a neurotransmitter that, at high levels, becomes toxic. This excess kills neurons and inflames surrounding brain tissue, helping the tumor thrive," says Borges.

In addition to bioluminescence, the researchers used PET scan, a technology already employed in hospitals, to track substances and test the effects of potential therapies. This combination forms a robust platform for understanding and interfering in cancer progression in the brain.

Science, Family, and Global Networks

The project is also remarkable for its human dimension: researchers Helena Borges and Stevens Rehen, who coordinate the study, are married - and admit their scientific discussions often extend into family life.

This partnership goes beyond the home, extending into a global research network. Collaborators include the University of Wisconsin-Madison, home to 19 Nobel Prize winners, and the biotech company Promega, which contributed with cell-detection technologies.

Next Steps: Therapies and Accessibility

One of the greatest strengths of this model is its accessibility: it can be adapted for laboratories without cutting-edge infrastructure, enabling more research centers in Brazil and abroad to test new treatments in realistic conditions.

"The platform is ready to be used for testing new chemotherapy drugs or compounds that could reduce the tumor's impact on the brain," Borges explains. "It faithfully simulates what happens in the body, with the advantage of allowing adjustments, observations, and controlled experiments."

The expectation is that, over time, this approach will help accelerate the development of personalized therapies, reduce brain damage, and increase survival rates for patients with metastatic cancer.