RRC ID 52441
著者 Mito A, Nakano Y, Saitoh T, Gouraud SSS, Yamaguchi Y, Sato T, Sasaki N, Kojima-Aikawa K.
タイトル Lectin ZG16p inhibits proliferation of human colorectal cancer cells via its carbohydrate-binding sites.
ジャーナル Glycobiology
Abstract Zymogen granule protein 16 (ZG16p) is a soluble lectin that binds to both mannose and heparin/heparan sulfate. It is highly expressed in the human digestive tract and is secreted into the mucus. In this study, we investigated the effect of ZG16p on the proliferation of human colorectal cancer cells. Overexpression of ZG16p in Caco-2 cells decreased cell growth. Recombinant ZG16p markedly inhibited proliferation of Caco-2, LS174T, HCT116 and HCT15 cells. Caco-2 cell growth was not inhibited by two mutated ZG16p proteins, D151A and M5 (K36A, R37A, R53A, R55A and R79A) lacking mannose- and heparin-binding activities, respectively. Immunofluorescent cell staining revealed that ZG16p-D151A maintained its binding to the Caco-2 cell surface, whereas ZG16p-M5 failed to bind to the cells. These results suggest that ZG16p interacts with the cell surface via basic amino acids substituted in ZG16p-M5 and inhibits Caco-2 cell proliferation via Asp151. In addition, growth of patient-derived colorectal tumor organoids in a 3D intestinal stem cell system was suppressed by ZG16p but not by ZG16p-M5. Taken together, our findings indicate that ZG16p inhibits the growth of colorectal cancer cells via its carbohydrate-binding sites in vitro and ex vivo. In this study, a novel pathway in cancer cell growth regulation through cell surface carbohydrate chains is suggested.
巻・号 28(1)
ページ 21-31
公開日 2018-12-1
DOI 10.1093/glycob/cwx088
PII 4562381
PMID 29069492
MeSH Apoptosis / drug effects Binding Sites / drug effects Carbohydrates / chemistry* Cell Proliferation / drug effects Colonic Neoplasms / drug therapy* Colonic Neoplasms / metabolism Colonic Neoplasms / pathology* Humans Lectins / chemistry Lectins / metabolism* Tumor Cells, Cultured
IF 4.06
引用数 3
リソース情報
ヒト・動物細胞 CACO-2(RCB0988) HCT116(RCB2979)