Laboratory of glycobiology, The Noguchi Institute, Tokyo, 173-0033, Japan.
Department of Clinical Bio-resource Research and Development, Graduate School of Medicine, Kyoto University, Kyoto, 606-8501, Japan.
Sci Rep. 2020 Feb 17;10(1):2708. doi: 10.1038/s41598-020-59622-y.
Prostate-specific antigen (PSA) is the most frequently used biomarker for the screening of prostate cancer. Understanding the structure of cancer-specific glycans can help us improve PSA assay. In the present study, we analysed the glycans of PSA obtained from culture medium containing cancer tissue-originated spheroids (CTOS) which have similar characteristics as that of the parent tumour to explore the new candidates for cancer-related glycoforms of PSA. The glycan profile of PSA from CTOS was determined by comparing with PSA from normal seminal plasma and cancer cell lines (LNCaP and 22Rv1) using lectin chromatography and mass spectrometry. PSA from CTOS was mostly sialylated and the content of Wisteria floribunda agglutinin reactive glycan (LacdiNAc) was similar to that of PSA derived from seminal plasma and 22Rv1. Conversely, concanavalin A (Con A)-unbound PSA was definitely detected from the three cancer origins but was almost negligible in seminal PSA. Two novel types of PSA were elucidated in the Con A-unbound fraction: one is a high molecular weight PSA with highly branched N-glycans, and the other is a low molecular weight PSA without N-glycans. Furthermore, the existence of Lewis X antigen group on PSA was indicated. These PSAs will be candidates for new cancer-related markers.
前列腺特异性抗原（PSA）是前列腺癌筛查中最常用的生物标志物。了解癌症特异性聚糖的结构可以帮助我们改进 PSA 检测。在本研究中，我们分析了来自含有源自癌症组织球体（CTOS）的培养基中的 PSA 的聚糖，这些球体具有与亲本肿瘤相似的特征，以探索 PSA 的新的癌症相关糖型候选物。通过与正常精液 PSA 和癌细胞系（LNCaP 和 22Rv1）的 PSA 进行比较，使用凝集素色谱和质谱法确定了来自 CTOS 的 PSA 的聚糖谱。来自 CTOS 的 PSA 主要是唾液酸化的，并且 Wisteria floribunda 凝集素反应性聚糖（LacdiNAc）的含量与来自精液和 22Rv1 的 PSA 相似。相反，来自三种癌症来源的 CTOS 的 Con A 未结合 PSA 明显被检测到，但在精液 PSA 中几乎可以忽略不计。在 Con A 未结合部分中阐明了两种新型 PSA：一种是具有高度分支的 N-聚糖的高分子量 PSA，另一种是没有 N-聚糖的低分子量 PSA。此外，表明 PSA 上存在 Lewis X 抗原组。这些 PSA 将成为新的癌症相关标志物的候选物。
