Siglec-15 recognition of sialoglycans on tumor cell lines can occur independently of sialyl Tn antigen expression. (30th May 2020)

• Record Type: Journal Article
• Authors: Murugesan, Gavuthami; Correia, Viviana G; Palma, Angelina S; Chai, Wengang; Li, Chunxia; Feizi, Ten; Martin, Eva; Laux, Brigitte; Franz, Alexandra; Fuchs, Klaus; Weigle, Bernd; Crocker, Paul R
• Is Part Of: Glycobiology. Volume 31:Number 1(2021)
• Page Start: 44
• Page End: 54
• Publication Date: 2020-05-30
• Subjects: cancer -- sialic acid -- siglec; Glycoproteins -- Periodicals; Glycolipids -- Periodicals; Glycoconjugates -- Periodicals; 572.567
• DOI: 10.1093/glycob/cwaa048
• Languages: English
• ISSNs: 0959-6658

Abstract

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.