A single protein may help aggressive breast cancer spread to the brain and evade immune defenses

by Wake Forest University School of Medicine

edited by Robert Egan

Robert Egan

Senior Editor

Meet our editorial team
Behind our editorial process
Editors' notes

This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility:

fact-checked

trusted source

proofread

The GIST Add as preferred source

Researchers at Wake Forest University School of Medicine have identified a protein that may help an aggressive form of breast cancer spread to the brain and escape the body's immune defenses.

The study found that SIRPα, a protein best known for regulating immune cells, also appears to act inside triple-negative breast cancer cells. In preclinical models, higher levels of the protein made the cancer cells more likely to spread and weakened the brain's immune response against them.

The findings were recently published in Neuro-Oncology.

Triple-negative breast cancer, or TNBC, is an aggressive form of breast cancer that lacks three common markers used to guide treatment. It has a greater tendency than many other breast cancers to spread to the brain, where treatment options remain limited and outcomes are often poor.

The new findings offer a possible explanation for how TNBC cells establish tumors in the brain and identify SIRPα as a potential focus for future treatment research. The results are preclinical, however, and additional studies are needed before the approach can be evaluated in patients.

"The biology of brain metastasis is incredibly complex, and we urgently need better ways to prevent and treat it," said David R. Soto-Pantoja, Ph.D., corresponding author and associate professor of cancer biology at Wake Forest University School of Medicine. "Our findings suggest that SIRPα helps make tumor cells more aggressive while also changing the brain environment in ways that help those cells survive."

A protein with a surprising role

By examining human breast cancer data and tumor samples, researchers found higher levels of SIRPα in TNBC cells, particularly in tumors that had spread to the brain. Higher SIRPα levels were also associated with poorer outcomes among patients with TNBC.

Laboratory experiments suggested that SIRPα changes the behavior of mitochondria, the structures that produce energy within cells. In cancer cells with high levels of SIRPα, the mitochondria broke into smaller pieces through a process called mitochondrial fission. This change made the cancer cells more mobile and more likely to spread in the study models.

Helping cancer spread—and hide

The researchers also found that SIRPα increased production of fibronectin, a protein that helps provide structure and support around cells. Fibronectin appeared to weaken the response of microglia, immune cells that help protect the brain. With repeated exposure to fibronectin, the microglia became less able to trigger inflammation and attack the cancer cells.

"One of the most intriguing findings was that the tumor cells appeared to weaken the response of the brain's immune cells," Soto-Pantoja said. "This creates a more favorable environment for cancer cells to grow and survive, and SIRPα appears to play an important role in that process."

Putting the theory to the test

The researchers analyzed human breast cancer data and patient tumor samples and conducted experiments involving breast cancer cells, immune cells and mitochondria. They also used preclinical models designed to reproduce the spread of breast cancer to the brain.

Across several models, reducing or inhibiting SIRPα slowed tumor growth, decreased the amount of cancer found in the brain and delayed the development of brain metastases. It also reversed some of the changes that helped cancer cells evade the brain's immune response.

What this could mean for treatment

Most experimental treatments involving the CD47-SIRPα pathway have focused on its role in immune cells. These findings suggest that targeting SIRPα could potentially have an additional effect by interfering directly with processes inside cancer cells that help them spread.

The study also connects several biological processes involved in brain metastasis, including changes in how cancer cells produce energy, their surrounding structural environment and the brain's immune response. Understanding how these processes work together could inform future treatment research for patients with TNBC that has spread, or is at high risk of spreading, to the brain.

The next questions researchers hope to answer

The investigators plan to continue studying how SIRPα functions in cancer cells and whether it can be safely targeted. Future studies will also explore whether blocking SIRPα could enhance existing immunotherapies or other treatments for TNBC brain metastases.

More information

Yu-Ting Tsai et al, Cancer-intrinsic SIRPα Signaling Triggers Mitochondrial Fission and Immune Tolerance to Promote TNBC Breast-to-Brain Metastasis, Neuro-Oncology (2026). DOI: 10.1093/neuonc/noag202

Key medical concepts

Triple Negative Breast NeoplasmsBrain MetastaseFibronectin

Clinical categories

OncologyWomen's healthNeurology Provided by Wake Forest University School of Medicine Who's behind this story?

Robert Egan

Bachelor's in mathematical biology, Master's in creative writing. Well-traveled with unique perspectives on science and language. Full profile →

Citation: A single protein may help aggressive breast cancer spread to the brain and evade immune defenses (2026, September 18) retrieved 18 September 2026 from https://medicalxpress.com/news/2026-09-protein-aggressive-breast-cancer-brain.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.