RRC ID 51792
Author Zhou J, You W, Sun G, Li Y, Chen B, Ai J, Jiang H.
Title 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.
Journal J Pharmacol Exp Ther
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.
Volume 359(1)
Pages 54-61
Published 2016-10
DOI 10.1124/jpet.116.234799
PII jpet.116.234799
PMID 27432893
MeSH Animals Apoptosis / drug effects CD8-Positive T-Lymphocytes / drug effects CD8-Positive T-Lymphocytes / immunology Cell Line, Tumor Cell Movement / drug effects Cell Transformation, Neoplastic Epithelial-Mesenchymal Transition / drug effects* Female Humans Mice Neoplasm Invasiveness Neoplasm Metastasis Oligosaccharides / pharmacology* Signal Transduction / drug effects Smad Proteins / metabolism Transforming Growth Factor beta1 / antagonists & inhibitors* Transforming Growth Factor beta1 / pharmacology*
IF 3.615
Times Cited 6
Human and Animal Cells MKN45(RCB1001)