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

Citation:
Murugesan, Gavuthami, Viviana G. Correia, Angelina S. Palma, Wengang Chai, Chunxia Li, Ten Feizi, Eva Martin, Brigitte Laux, Alexandra Franz, Klaus Fuchs, Bernd Weigle, and Paul R. Crocker. "Siglec-15 recognition of sialoglycans on tumor cell lines can occur independently of sialyl Tn antigen expression." Glycobiology (2020).

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-$\beta$. 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-$\beta$ 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.

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