Role of Biomarker in Predicting and Driving Brain Metastasis in Inflammatory Breast Cancer

By: Emily Rhode
Posted: Friday, January 27, 2023

According to Xiaoding Hu, PhD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues, patients with inflammatory breast cancer (IBC) may be more likely to develop brain metastases and therefore have poorer survival rates. The results of their recent study, presented during the 2022 San Antonio Breast Cancer Symposium Annual Meeting (Abstract GS5-08), bring to light the unique role of the tumor promotor, soluble E-cadherin (Ecad), in tumor growth and brain metastases development.

Serum soluble Ecad levels of 348 patients with IBC were analyzed using an enzyme-linked immunosorbent assay. SUM149 cells, MDA-IBC3 cells, human brain microvascular endothelial cells, and immortalized human astrocytes were used in vivo in mouse models and in vitro to study tumor growth and brain metastasis. Higher serum soluble Ecad levels were correlated with the development of brain metastasis (P = .04), earlier development of metastasis (P = .006), and poorer overall survival (P = .02). Multivariable analysis revealed that soluble Ecad levels independently predicted overall survival (hazard ratio = 2.07; P = .01).

Moreover, the researchers found that soluble Ecad levels increased cancer cell adhesion to brain endothelial cells (P = .01) and promoted the induction of reactive astrocytes. Mass spectrometry and Bio-ID assays showed that soluble Ecad binds with X-linked inhibitor of apoptosis protein (XIAP). Finally, analysis of RNA-sequence profiling data as well as immunoblotting revealed that soluble Ecad seems to activate the NF-kB inflammatory signaling pathway. The researchers hypothesized that XIAP could induce NF-kB activation to inhibit cell apoptosis in breast cancer cells.

These results highlight the role of soluble Ecad in promoting brain metastasis in IBC, providing a possible prognostic indicator and potential therapeutic targets.

Disclosure: For full disclosures of the study authors, visit sabcs.org.

2022 San Antonio Breast Cancer Symposium

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