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

TY - JOUR

T1 - Siglec-15 recognition of sialoglycans on tumor cell lines can occur independently of sialyl Tn antigen expression

AU - Murugesan, Gavuthami

AU - Correia, Viviana G.

AU - Palma, Angelina S.

AU - Chai, Wengang

AU - Li, Chunxia

AU - Feizi, Ten

AU - Martin, Eva

AU - Laux, Brigitte

AU - Franz, Alexandra

AU - Fuchs, Klaus

AU - Weigle, Bernd

AU - Crocker, Paul R.

N1 - Funding: March of Dimes Foundation, (Grant / Award Number: '22-FY18-821') Portuguese Foundation for Science and Technology , (Grant / Award Number: 'PTDC/BIA-MIB/31730/2017','UID/Multi/04378/2019'); Wellcome Trust, (Grant / Award Number: '103744/Z/14/Z ','108430/Z/15/Z')

PY - 2021/1

Y1 - 2021/1

N2 - 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.

AB - 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.

KW - cancer

KW - sialic acid

KW - siglec

UR - https://www.scopus.com/pages/publications/85100069840

U2 - 10.1093/glycob/cwaa048

DO - 10.1093/glycob/cwaa048

M3 - Article

C2 - 32501471

SN - 0959-6658

VL - 31

SP - 44

EP - 54

JO - Glycobiology

JF - Glycobiology

IS - 1

ER -