The marine-derived oligosaccharide sulfate MS80, a novel transforming growth factor b1 inhibitor, reverses epithelial mesenchymal transition induced by transforming growth factor-b1 and suppresses tumor metastasiss

Abstract

Metastasis accounts for the majority of cancer-related deaths. Transforming growth factor b (TGF-b) 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 TGFb1-induced pulmonary fibrosis by binding TGF-b1. In our study MS80 effectively inhibited TGF-b/Smad signaling in lung cancer cells, breast cancer cells, and model cell lines. In addition, MS80 inhibited TGF-b1-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 CD81 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-b1-induced EMT and mediating immunosuppression.