Protein SIRPα Identified as Key Factor in Triple-Negative Breast Cancer Brain Metastasis

Wake Forest University researchers identified SIRPα, a protein regulating immune cells, as playing a critical role in enabling triple-negative breast cancer to spread to the brain and evade immune defenses. Preclinical studies demonstrated that reducing or blocking SIRPα slowed tumor growth, decreased brain cancer presence, and delayed metastases development, while reversing immune evasion mechanisms. Analysis of patient tumor samples revealed elevated SIRPα levels in triple-negative breast cancer tumors that had metastasized to the brain, correlating with poorer patient outcomes.

Triple-negative breast cancer presents a particularly aggressive clinical challenge because it lacks the hormone receptors and growth factor markers that typically guide treatment decisions for other breast cancers. This absence of targetable features makes the disease harder to manage, and patients face especially poor prognosis when metastases develop in the brain, where drug delivery and immune activity both face significant obstacles.

The research team discovered that SIRPα functions on multiple biological levels simultaneously. Beyond its known role in immune regulation, the protein appears to trigger structural changes in cancer cells' energy centers, making them more mobile and invasive. Simultaneously, it stimulates production of fibronectin, which gradually impairs the brain's resident immune cells' ability to mount effective defenses against the spreading tumors.