Patients with inflammatory breast cancer (IBC) are more likely to develop brain metastases, which leads to poor survival rates.
There is a critical unmet need to understand this increased risk in order to improve patient outcomes.
Researchers led by Xiaoding Hu, MD, PhD, and Bisrat Debeb, DVM, PhD, sought to uncover the possible role of soluble E-cadherin (sEcad) in the development and progression of brain metastases.
By analysing serum levels of sEcad in 348 IBC patients, researchers found higher levels correlated with lower overall survival (OS) as well as earlier and increased development of brain metastases.
Additionally, overexpressing sEcad in laboratory models promoted primary tumour growth and shortened OS, with a significant increase in the incidence of brain metastases, metastatic burden and number of metastases.
Further analysis showed that sEcad increases cancer cell adhesion to brain cells, promotes the induction of harmful reactive astrocytes, binds with and activates a known inhibitor of cell death, and activates the NF-kB inflammatory signaling pathway.
These results highlight the role of sEcad in promoting brain metastasis in IBC, providing a possible prognostic indicator and potential therapeutic targets.
Hu will present the results on December 9.