Siglec-15 recognition of sialoglycans on tumor cell lines can occur independently of sialyl Tn antigen expression

Gavuthami Murugesan, Viviana G. Correia, Angelina S. Palma, Wengang Chai, Chunxia Li, Ten Feizi, Eva Martin, Brigitte Laux, Alexandra Franz, Klaus Fuchs, Bernd Weigle, Paul R. Crocker (Lead / Corresponding author)

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Abstract

Siglec-15 is a conserved sialic acid-binding Ig-like lectin expressed on osteoclast progenitors that 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 cells 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 languageEnglish
Article numbercwaa048
Pages (from-to)1-11
Number of pages11
JournalGlycobiology
Early online date30 May 2020
DOIs
Publication statusE-pub ahead of print - 30 May 2020

Keywords

  • sialic acid
  • siglec
  • cancer

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    Murugesan, G., Correia, V. G., Palma, A. S., Chai, W., Li, C., Feizi, T., Martin, E., Laux, B., Franz, A., Fuchs, K., Weigle, B., & Crocker, P. R. (2020). Siglec-15 recognition of sialoglycans on tumor cell lines can occur independently of sialyl Tn antigen expression. Glycobiology, 1-11. [cwaa048]. https://doi.org/10.1093/glycob/cwaa048