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Abstract
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.
Original language | English |
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Pages (from-to) | 44-54 |
Number of pages | 11 |
Journal | Glycobiology |
Volume | 31 |
Issue number | 1 |
Early online date | 30 May 2020 |
DOIs | |
Publication status | Published - Jan 2021 |
Keywords
- cancer
- sialic acid
- siglec
ASJC Scopus subject areas
- Biochemistry
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Dive into the research topics of 'Siglec-15 recognition of sialoglycans on tumor cell lines can occur independently of sialyl Tn antigen expression'. Together they form a unique fingerprint.Projects
- 1 Finished
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Molecular Dissection of Siglec-Mediated Regulation of Neutrophil Inflammatory Responses (Senior Investigator Award)
Crocker, P. (Investigator)
1/08/14 → 31/12/19
Project: Research