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J Pharmacol Exp Ther. 2016 Oct;359(1):54-61. doi: 10.1124/jpet.116.234799. Epub 2016 Jul 18.

The Marine-Derived Oligosaccharide Sulfate MS80, a Novel Transforming Growth Factor β1 Inhibitor, Reverses Epithelial Mesenchymal Transition Induced by Transforming Growth Factor-β1 and Suppresses Tumor Metastasis.

Author information

1
Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (J.Z., G.S., Y.L., J.A.), and Department of Respiratory Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University (W.Y., B.C., H.J.), Shanghai, People's Republic of China.
2
Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (J.Z., G.S., Y.L., J.A.), and Department of Respiratory Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University (W.Y., B.C., H.J.), Shanghai, People's Republic of China jai@simm.ac.cn jianghd@163.com.

Abstract

Metastasis accounts for the majority of cancer-related deaths. Transforming growth factor β (TGF-β) is believed to promote late-stage cancer progression and metastasis by inducing epithelial-mesenchymal transition (EMT). We previously reported that MS80, a novel oligosaccharide sulfate, inhibits TGF-β1-induced pulmonary fibrosis by binding TGF-β1. In our study MS80 effectively inhibited TGF-β/Smad signaling in lung cancer cells, breast cancer cells, and model cell lines. In addition, MS80 inhibited TGF-β1-induced EMT, motility, and invasion in vitro. Moreover, MS80 significantly inhibited lung metastasis in orthotopic 4T1 xenografts. Notably, the MS80 treatment significantly increased the infiltration of CD8(+) T cells and decreased the infiltration of regulatory T cells in primary tumors and spleens in mice bearing 4T1 xenografts. Therefore, MS80 is a novel and promising candidate for treating metastatic malignancies by targeting TGF-β1-induced EMT and mediating immunosuppression.

PMID:
27432893
DOI:
10.1124/jpet.116.234799
[Indexed for MEDLINE]

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