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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
- Source :
- The Journal of pharmacology and experimental therapeutics. 359(1)
- Publication Year :
- 2016
-
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.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Epithelial-Mesenchymal Transition
Oligosaccharides
Apoptosis
Smad Proteins
SMAD
Biology
CD8-Positive T-Lymphocytes
Metastasis
Transforming Growth Factor beta1
03 medical and health sciences
Mice
0302 clinical medicine
Cell Movement
Internal medicine
Cell Line, Tumor
medicine
Animals
Humans
Neoplasm Invasiveness
Epithelial–mesenchymal transition
Neoplasm Metastasis
Lung cancer
Pharmacology
Endoglin
medicine.disease
030104 developmental biology
Endocrinology
Cell Transformation, Neoplastic
Cell culture
030220 oncology & carcinogenesis
Cancer research
Molecular Medicine
Female
CD8
Transforming growth factor
Signal Transduction
Subjects
Details
- ISSN :
- 15210103
- Volume :
- 359
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- The Journal of pharmacology and experimental therapeutics
- Accession number :
- edsair.doi.dedup.....e2182ad75a0fc493aaf4ca96e30f0de5