与表达Globo H的细胞结合的天然抗聚糖抗体可识别卵巢癌患者。
Naturally occurring anti-glycan antibodies binding to Globo H-expressing cells identify ovarian cancer patients.
作者信息
Pochechueva Tatiana, Alam Shahidul, Schötzau Andreas, Chinarev Alexander, Bovin Nicolai V, Hacker Neville F, Jacob Francis, Heinzelmann-Schwarz Viola
机构信息
Ovarian Cancer Research, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
Glyco-Oncology, Ovarian Cancer Research, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
出版信息
J Ovarian Res. 2017 Feb 10;10(1):8. doi: 10.1186/s13048-017-0305-8.
BACKGROUND
Glycosphingolipids are important compounds of the plasma membrane of mammalian cells and a number of them have been associated with malignant transformation and progression, reinforcing tumour aggressiveness and metastasis. Here we investigated the levels of naturally occurring anti-glycan antibodies to Globo H in blood plasma obtained from high-grade serous ovarian cancer patients (SOC) and women without gynaecological malignancies (control) using suspension glycan array technology employing chemically synthesized glycans as antibody targets.
RESULTS
We found that anti-human Globo H IgG antibodies were able to significantly discriminate SOC from controls (P < 0.05). A combination with the clinically used tumour marker CA125 increased the diagnostic performance (AUC 0.8711). We next compared suspension array with standard flow cytometry in plasma samples and found that the level of anti-Globo H antibodies highly correlated (r = 0.992). The incubation of plasma-derived anti-glycan antibodies with chemically synthesized (presented on fluorescence microspheres) and native Globo H (expressed on Globo H-positive cell lines) revealed strong reactivity of naturally occurring human anti-Globo H antibodies towards its antigen expressed on ovarian cancer cells.
CONCLUSIONS
Our data demonstrate that human plasma-derived antibodies to Globo H as well as the presence of the antigen might be considered as therapeutic option in ovarian cancer.
背景
糖鞘脂是哺乳动物细胞质膜的重要化合物，其中一些与恶性转化和进展相关，增强了肿瘤的侵袭性和转移性。在此，我们使用以化学合成聚糖为抗体靶点的悬浮聚糖阵列技术，研究了从高级别浆液性卵巢癌患者（SOC）和无妇科恶性肿瘤的女性（对照）获得的血浆中天然存在的抗Globo H聚糖抗体的水平。
结果
我们发现抗人Globo H IgG抗体能够显著区分SOC和对照（P < 0.05）。与临床使用的肿瘤标志物CA125联合使用可提高诊断性能（AUC 0.8711）。接下来，我们比较了血浆样本中的悬浮阵列和标准流式细胞术，发现抗Globo H抗体水平高度相关（r = 0.992）。血浆来源的抗聚糖抗体与化学合成的（呈现在荧光微球上）和天然的Globo H（在Globo H阳性细胞系上表达）孵育，揭示了天然存在的人抗Globo H抗体对卵巢癌细胞上表达的其抗原具有强烈反应性。
结论
我们的数据表明，人血浆来源的抗Globo H抗体以及抗原的存在可能被视为卵巢癌的一种治疗选择。
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