Siglec-15 recognition of sialoglycans on tumor cell lines can occur independently of sialyl Tn antigen expression
| Autor: | Alexandra Franz, Gavuthami Murugesan, Brigitte Laux, Klaus Fuchs, Bernd Weigle, Chunxia Li, Angelina S. Palma, Ten Feizi, Eva Martin, Paul R. Crocker, Wengang Chai, Viviana G. Correia |
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| Rok vydání: | 2020 |
| Předmět: |
medicine.drug_class
AcademicSubjects/SCI01000 Immunoglobulins Syk Monoclonal antibody Biochemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Antigen Polysaccharides Tumor Cells Cultured medicine cancer Humans Antigens Tumor-Associated Carbohydrate Avidity Progenitor cell Cancer Biology 030304 developmental biology 0303 health sciences biology Membrane Proteins SIGLEC respiratory system siglec Coculture Techniques Cell biology Sialic acid chemistry sialic acid 030220 oncology & carcinogenesis Sialic Acids biology.protein Antibody |
| Zdroj: | Glycobiology |
| ISSN: | 1460-2423 |
| Popis: | Siglec-15 is a conserved sialic acid-binding Ig-like lectin expressed on osteoclast progenitors, which plays an important role in osteoclast development and function. It is also expressed by tumor-associated macrophages and by some tumors, where it is thought to contribute to the immunosuppressive microenvironment. It was shown previously that engagement of macrophage-expressed Siglec-15 with tumor cells expressing its ligand, sialyl Tn (sTn), triggered production of TGF-β. In the present study, we have further investigated the interaction between Siglec-15 and sTn on tumor cells and its functional consequences. Based on binding assays with lung and breast cancer cell lines and glycan-modified cells, we failed to see evidence for recognition of sTn by Siglec-15. However, using a microarray of diverse, structurally defined glycans, we show that Siglec-15 binds with higher avidity to sialylated glycans other than sTn or related antigen sequences. In addition, we were unable to demonstrate enhanced TGF-β secretion following co-culture of Siglec-15-expressing monocytic cell lines with tumor cells expressing sTn or following Siglec-15 cross-linking with monoclonal antibodies. However, we did observe activation of the SYK/MAPK signaling pathway following antibody cross-linking of Siglec-15 that may modulate the functional activity of macrophages. |
| Databáze: | OpenAIRE |
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