Fucoidan suppresses the gastric cancer cell malignant phenotype and production of TGF-β1 via CLEC-2

Author:

Xu Ling12,Liu Fenglin3,Li Can12,Li Shuxuan12,Wu Hao12,Guo Bao12,Gu Jianxin12,Wang Lan12

Affiliation:

1. NHC Key Laboratory of Glycoconjugate Research, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China

2. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China

3. Department of General Surgery, Zhongshan Hospital, 180 Fenglin Road, Fudan University, Shanghai 20032, China

Abstract

Abstract 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-β1) 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-β1 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.

Funder

National Key Research and Development Program of China

National Natural Science Foundation of China

Research Fund Program of Shandong Provincial Key Laboratory of Glycoscience & Glycotechnology

Publisher

Oxford University Press (OUP)

Subject

Biochemistry

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