RRC ID 63701
著者 Ito N, Yamada M, Morishita K, Nojima S, Motooka K, Sakata N, Asuka T, Otsu R, Takamatsu S, Kamada Y, Mori S, Akita H, Eguchi H, Morii E, Miyoshi E.
タイトル Identification of fucosylated haptoglobin-producing cells in pancreatic cancer tissue and its molecular mechanism.
ジャーナル Glycoconj J
Abstract 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.
巻・号 38(1)
ページ 45-54
公開日 2021-2-1
DOI 10.1007/s10719-020-09970-8
PII 10.1007/s10719-020-09970-8
PMID 33523362
MeSH Cell Differentiation / drug effects Cell Line, Tumor Culture Media, Conditioned / chemistry Gene Expression Regulation / drug effects Glycosylation Haptoglobins / metabolism* Humans Immunohistochemistry / methods Leukemia / metabolism Leukemia / pathology Macrophages / cytology Pancreatic Neoplasms / metabolism* Pancreatic Neoplasms / pathology Protein Precursors / metabolism THP-1 Cells Tetradecanoylphorbol Acetate / pharmacology Tumor Microenvironment
IF 2.197
リソース情報
ヒト・動物細胞 THP-1 PANC-1(RCB2095) Hep G2(RCB1648)