Department for Immunochemistry and Glycobiology, Institute for the Application of Nuclear Energy - INEP, University of Belgrade, Belgrade, Serbia.
Dis Markers. 2012;32(3):187-94. doi: 10.3233/DMA-2011-0872.
This study was aimed at obtaining insight into the diversity of sialic acids in cancer- and non-cancer-related CA125 antigen, tumour marker of serous ovarian cancer. Starting from available data suggesting the possible relevance of sialic acids for discriminating CA125 antigens of different origin, we have employed a new experimental approach based on the use of human sialic acid-binding Ig-like lectins, Siglecs, as tools for the investigation of sialylation. Siglec-2, belonging to the group of evolutionarily conserved Siglecs, and Siglec-3, -6, -7, -9 and -10, which are CD33-like Siglecs, were probed in solid-phase binding assays with cancer-related CA125 antigens from pleural fluid of patients with ovarian carcinoma (pfCA125), the OVCAR-3 ovarian carcinoma cell line (clCA125) and a non-cancer-related CA125 antigen, i.e. pregnancy-associated pCA125 antigen. All Siglecs used showed detectable binding to pCA125 antigen. Siglec-3, Siglec-7 and Siglec-2 exhibited moderately stronger binding to pCA125 antigen than the others. In contrast to this, Siglec-2 and Siglec-3 preferentially recognized pfCA125 with greater total binding than for pCA125, whereas Siglec-9 and Siglec-10 were highly selective for clCA125. Siglecs promise to be powerful tools for discriminating CA125 of different origin and could propagate further research on other molecular markers of biomedical and diagnostic importance.
本研究旨在深入了解癌症相关和非癌症相关 CA125 抗原(卵巢浆液性癌的肿瘤标志物)中唾液酸的多样性。鉴于已有数据表明唾液酸可能与区分不同来源的 CA125 抗原有关,我们采用了一种新的实验方法,基于使用人唾液酸结合免疫球蛋白样凝集素(Siglecs)作为研究唾液酸化的工具。Siglec-2 属于进化上保守的 Siglecs 组,而 Siglec-3、-6、-7、-9 和 -10 则属于 CD33 样 Siglecs。在固相结合实验中,我们用来自卵巢癌患者胸腔积液中的癌症相关 CA125 抗原(pfCA125)、OVCAR-3 卵巢癌细胞系(clCA125)和非癌症相关 CA125 抗原(即妊娠相关 pCA125 抗原)对这些 Siglecs 进行了探测。所有使用的 Siglecs 均显示出可检测到的与 pCA125 抗原的结合。Siglec-3、Siglec-7 和 Siglec-2 与 pCA125 抗原的结合程度比其他 Siglecs 略强。与此相反,Siglec-2 和 Siglec-3 优先识别 pfCA125,总结合量大于 pCA125,而 Siglec-9 和 Siglec-10 则高度选择性地识别 clCA125。Siglecs 有望成为区分不同来源 CA125 的有力工具,并能进一步推动对其他具有生物医学和诊断重要性的分子标志物的研究。