First Evidence for a Role of Siglec-8 in Breast Cancer

• Main Authors: Anna Trebo, Nina Ditsch, Tom Degenhardt, Christina Kuhn, Martina Rahmeh, Elisa Schmoeckel, Doris Mayr, Bastian Czogalla, Thomas Kolben, Sarah Meister, Sven Mahner, Udo Jeschke, Anna Hester
• Format: Article
• Language: English
• Published: MDPI AG 2021-02-01
• Series: International Journal of Molecular Sciences
• Subjects: breast cancer; Siglec; Siglec-8; PPARγ; Gal-7; TA-MUC1
• Online Access: https://www.mdpi.com/1422-0067/22/4/2000
• ISSN: 1661-6596; 1422-0067

Sialic acid-binding immunoglobulin-like lectins (Siglecs) are involved in various immune cell-mediated diseases. Their role in cancer is poorly investigated, and research focusses on Siglec-expression on immune cells interacting with tumor cells. This study evaluates the role of Siglec-8 in breast cancer (BC). Siglec-8 expression was analyzed immunohistochemically on 235 primary BC cases and was correlated with clinical and pathological parameters and outcome. Cell culture experiments were performed with various BC cell lines. Siglec-8 was expressed in 215 BC cases and expression was lowest in triple-negative BC. It correlated with estrogen receptor-status, grading and the prognostic factors galectin (Gal)-7 and tumor-associated mucin-1 (TA-MUC1). However, Gal-7 and TA-MUC1 were only prognosticators for clinical outcome in the cohort expressing high (Immunoreactivity score IRS > 3) Siglec-8 levels but not in the low-expressing cohort. Siglec-8 knockdown led to a significantly reduced Gal-7 expression in MCF7 cells. All BC cell lines expressed low Siglec-8-levels, that could be elevated in MCF7 by Peroxisome proliferator-activated receptor (PPARγ)-stimulation. This study demonstrates that Siglec-8 is expressed in BC cells and correlates with known clinical and prognostic parameters. It is probably associated with Gal-7 and TA-MUC1 and might be regulated via PPARγ. Further analyses focusing on functional associations will clarify Siglec-8’s eligibility as a possible therapeutic target.