Fucosylated haptoglobin is a well-established glyco-biomarker of pancreatic cancer. We recently established a novel anti-glycan antibody (10-7G mAb) that specifically recognizes fucosylated haptoglobins, including prohaptoglobin (proHpt). Serum concentrations of the 10-7G value, as measured by ELISA, were increased in patients with pancreatic cancer relative to the healthy controls. However, it is currently unknown which specific tissue or cell type produces fucosylated haptoglobins or proHpt. In the present study, we performed immunohistochemical (IHC) and ELISA analyses of pancreatic cancer tissue samples using 10-7G mAb. Among 21 pancreatic tissue sections, only 1 showed direct staining of pancreatic cells with the 10-7G mAb. However, 12 of the 21 sections stained positively for immune cells. Although there was no significant difference in the 10-7G expression between the positive and negative staining IHC groups, the median value of serum 10-7G was slightly higher in IHC-positive cases. Among many assayed leukemic cell lines, differentiated THP-1 cells (a human acute monocytic leukemia cell line) were found to have the highest levels of proHpt, per Western blot using 10-7G mAb. Interestingly, production of proHpt in vitro was dramatically increased under either hypoxic conditions or after IL-6 treatment. These results suggest that immune cells, including macrophages, in the pancreatic tissue microenvironment produce fucosylated haptoglobin and proHpt. Thus, fucosylated haptoglobins can be detected by the 10-7G mAb and may be a promising biomarker for pancreatic cancer.

岩藻糖基化结合珠蛋白是一种公认​​的胰腺癌糖生物标志物。我们最近建立了一种新的抗聚糖抗体 (10-7G mAb)，它专门识别岩藻糖基化的触珠蛋白，包括触珠蛋白原 (proHpt)。通过 ELISA 测量的 10-7G 值的血清浓度在胰腺癌患者中相对于健康对照组有所增加。然而，目前尚不清楚哪种特定组织或细胞类型会产生岩藻糖基化触珠蛋白或 proHpt。在本研究中，我们使用 10-7G mAb 对胰腺癌组织样本进行了免疫组织化学 (IHC) 和 ELISA 分析。在 21 个胰腺组织切片中，只有 1 个显示胰腺细胞用 10-7G mAb 直接染色。然而，21 个切片中有 12 个对免疫细胞染色呈阳性。尽管 IHC 染色阳性组和阴性染色组之间 10-7G 表达无显着差异，但 IHC 阳性病例血清 10-7G 的中值略高。在许多检测的白血病细胞系中，使用 10-7G mAb 进行的每个蛋白质印迹发现分化的 THP-1 细胞（人类急性单核细胞白血病细胞系）具有最高水平的 proHpt。有趣的是，proHpt 的生产在缺氧条件下或 IL-6 处理后，体外显着增加。这些结果表明，胰腺组织微环境中的免疫细胞，包括巨噬细胞，会产生岩藻糖基化的触珠蛋白和 proHpt。因此，岩藻糖基化的触珠蛋白可以被 10-7G mAb 检测到，并且可能是胰腺癌的有前途的生物标志物。