Fucoidan suppresses the gastric cancer cell malignant phenotype and production of TGF-β1 via CLEC-2.
Glycobiology. 2019 Nov 19. Epub 2019 Nov 19. PMID: 31742327
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 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 CDX2, an important regulator of gut homeostasis. In addition, the inhibitory effect of fucoidan on the gastric cancer 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 anti-tumorigenesis and anti-metastatic activity, suggesting that fucoidan is a promising treatment for gastric carcinoma.