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

• DOI: 10.1124/jpet.116.234799
• Publication Date: 2016-07-19T01:59:18Z
• Authors: Ji Zhou; Wenjie You; Guangqiang Sun; Yixuan Li; Bi Chen; Jing Ai; Handong Jiang
• Keywords: 0301 basic medicine; Epithelial-Mesenchymal Transition; Oligosaccharides; Apoptosis; Smad Proteins; CD8-Positive T-Lymphocytes; 3. Good health; Transforming Growth Factor beta1; Mice; 03 medical and health sciences; Cell Transformation, Neoplastic; Cell Movement; Cell Line, Tumor; Animals; Humans; Female; Neoplasm Invasiveness; Neoplasm Metastasis; Signal Transduction

Metastasis accounts for the majority of cancer-related deaths. Transforming growth factor <i>β</i> (TGF-<i>β</i>) 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-<i>β</i>1–induced pulmonary fibrosis binding TGF-<i>β</i>1. In our study MS80 effectively inhibited TGF-<i>β</i>/Smad signaling in lung cells, breast model cell lines. addition, EMT, motility, invasion vitro. Moreover, significantly orthotopic 4T1 xenografts. Notably, treatment increased infiltration CD8⁺ T cells decreased regulatory primary tumors spleens mice bearing Therefore, promising candidate treating metastatic malignancies targeting EMT mediating immunosuppression.