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

Abstract

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.

• 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
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 4 (Feb 18 2021) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 33670444 (Publication Type: Journal Article)

Chemical References

• Antigens, CD
• Antigens, Differentiation, B-Lymphocyte
• Galectins
• LGALS7 protein, human
• Lectins
• MUC1 protein, human
• Mucin-1
• Receptors, Estrogen
• SIGLEC8 protein, human

Topics

• Adult
• Aged
• Antigens, CD (biosynthesis, genetics)
• Antigens, Differentiation, B-Lymphocyte (biosynthesis, genetics)
• Breast Neoplasms (diagnosis, genetics, metabolism)
• Cell Line, Tumor
• Galectins (biosynthesis)
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry (methods)
• Lectins (biosynthesis, genetics)
• MCF-7 Cells
• Middle Aged
• Mucin-1 (biosynthesis)
• Neoplasm Grading
• Prognosis
• Receptors, Estrogen (metabolism)