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Lectin ZG16p inhibits proliferation of human colorectal cancer cells via its carbohydrate-binding sites
Glycobiology ( IF 4.3 ) Pub Date : 2017-10-23 , DOI: 10.1093/glycob/cwx088
Akiko Mito 1, 2 , Yukiko Nakano 1 , Takako Saitoh 1 , Sabine S S Gouraud 3 , Yoshiki Yamaguchi 4 , Toshiro Sato 5 , Nobuo Sasaki 5 , Kyoko Kojima-Aikawa 6, 7
Affiliation  

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.

中文翻译:

凝集素ZG16p通过其碳水化合物结合位点抑制人结肠直肠癌细胞的增殖

Zymogen颗粒蛋白16(ZG16p)是一种可溶性凝集素,可与甘露糖和肝素/硫酸乙酰肝素结合。它在人的消化道中高度表达,并分泌到粘液中。在这项研究中,我们研究了ZG16p对人结肠直肠癌细胞增殖的影响。ZG16p在Caco-2细胞中的过表达降低了细胞的生长。重组ZG16p明显抑制Caco-2,LS174T,HCT116和HCT15细胞的增殖。Caco-2细胞的生长不受两种分别缺乏甘露糖和肝素结合活性的突变ZG16p蛋白D151A和M5(K36A,R37A,R53A,R55A和R79A)抑制。免疫荧光细胞染色显示ZG16p-D151A保持其与Caco-2细胞表面的结合,而ZG16p-M5未能与细胞结合。这些结果表明,ZG16p通过在ZG16p-M5中取代的碱性氨基酸与细胞表面相互作用,并通过Asp151抑制Caco-2细胞的增殖。此外,ZG16p抑制了患者衍生的结肠直肠肿瘤类器官在3D肠道干细胞系统中的生长,但ZG16p-M5却没有抑制这种生长。两者合计,我们的发现表明ZG16p通过其碳水化合物结合位点在体外和离体抑制大肠癌细胞的生长。在这项研究中,提出了通过细胞表面碳水化合物链调节癌细胞生长的新途径。我们的发现表明,ZG16p通过其碳水化合物结合位点在体外和离体抑制大肠癌细胞的生长。在这项研究中,提出了通过细胞表面碳水化合物链调节癌细胞生长的新途径。我们的发现表明,ZG16p通过其碳水化合物结合位点在体外和离体抑制大肠癌细胞的生长。在这项研究中,提出了通过细胞表面碳水化合物链调节癌细胞生长的新途径。
更新日期:2017-10-23
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