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.

中文翻译：

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Siglec-15 对肿瘤细胞系上唾液酸聚糖的识别可以独立于唾液酸 Tn 抗原表达而发生。


Siglec-15是一种在破骨细胞祖细胞上表达的保守的唾液酸结合Ig样凝集素，在破骨细胞的发育和功能中发挥重要作用。它也由肿瘤相关巨噬细胞和一些肿瘤表达，被认为有助于免疫抑制微环境。之前的研究表明，巨噬细胞表达的 Siglec-15 与表达其配体唾液酸 Tn (sTn) 的肿瘤细胞结合，触发了 TGF-β 的产生。在本研究中，我们进一步研究了 Siglec-15 和 sTn 对肿瘤细胞的相互作用及其功能后果。根据对肺癌和乳腺癌细胞系以及聚糖修饰细胞的结合测定，我们未能看到 Siglec-15 识别 sTn 的证据。然而，通过使用多种结构明确的聚糖的微阵列，我们发现 Siglec-15 以更高的亲和力与除 sTn 或相关抗原序列之外的唾液酸化聚糖结合。此外，我们无法证明表达 Siglec-15 的单核细胞系与表达 sTn 的肿瘤细胞共培养后或 Siglec-15 与单克隆抗体交联后 TGF-β 分泌增强。然而，我们确实观察到 Siglec-15 抗体交联后 SYK/MAPK 信号通路的激活，可能调节巨噬细胞的功能活性。