Fucoidan suppresses the gastric cancer cell malignant phenotype and production of TGF-β1 via CLEC-2
Fucoidan suppresses the gastric cancer cell malignant phenotype and production of TGF-β1 via CLEC-2
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褐藻糖胶通过 CLEC-2 抑制胃癌细胞恶性表型和 TGF-β1 的产生
DOI：
10.1093/glycob/cwz097
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发表时间：
2020-05-01
期刊：
影响因子：
4.3
通讯作者：
Wang, Lan
中科院分区：
文献类型：
--
作者：
Xu, Ling;Liu, Fenglin;Wang, Lan
岩藻依聚糖硫酸酯在多种癌症中表现出优异的抗癌特性和低毒性。然而，其在胃癌中的详细药理作用和作用机制仍不清楚。在这项研究中，我们发现褐藻糖胶可以抑制胃癌（GC）细胞的生长，以及细胞的迁移和侵袭。细胞因子表达筛选表明，岩藻聚糖处理的细胞中转化生长因子β 1（TGF-β 1）分泌减少。岩藻依聚糖是血小板C型凝集素样受体2（CLEC-2）的激动剂，我们以前的研究发现，CLEC-2的上调抑制GC进展。在这里，我们证实，岩藻依聚糖，结合CLEC-2，显着增加CLEC-2的表达在GC细胞通过转录因子尾型同源框转录因子2，一个重要的调节肠道内稳态。此外，岩藻依聚糖对GC细胞恶性表型和TGF-β 1分泌的抑制作用可以通过敲低CLEC-2来恢复。因此，我们的数据表明，岩藻依聚糖靶向CLEC-2发挥抗肿瘤和抗转移活性，这表明岩藻依聚糖是一个有前途的治疗胃癌。
The sulfated polysaccharide fucoidan displays excellent anticancer properties with low toxicity in many kinds of cancers. However, its detailed pharmacological effect and mechanism of action in gastric carcinoma remains unclear. In this study, we found that fucoidan could suppress gastric cancer (GC) cell growth, as well as cell migration and invasion. A cytokine expression screen demonstrated that transforming growth factor beta 1 (TGF-beta 1) secretion was decreased in fucoidan-treated cells. Fucoidan has been reported to be a platelet agonist for the C-type lectin-like receptor 2 (CLEC-2), and our previous research found that upregulation of CLEC-2 inhibited GC progression. Here, we confirmed that fucoidan, combined with CLEC-2, significantly increased CLEC-2 expression in GC cells via the transcription factor caudal type homeobox transcription factor 2, an important regulator of gut homeostasis. In addition, the inhibitory effect of fucoidan on the GC cell malignant phenotype and TGF-beta 1 secretion could be restored by knocking down CLEC-2. Thus, our data suggest that fucoidan targets CLEC-2 to exert antitumorigenesis and antimetastatic activity, suggesting that fucoidan is a promising treatment for gastric carcinoma.