Anti-TGF-β attenuates tumor growth via polarization of tumor associated neutrophils towards an anti-tumor phenotype in colorectal cancer
| Autor: | Jifei Chen, Yan Zou, Liu Xiaoyong, Xiaoli Chen, Fengxian Qin, Huang Shishun, Kaifeng Deng, Wei Wei, Yujie Huang, Jianming Chen, Weijun Liang, Xuexiang Liu, Shanying Mo |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
phenotype colorectal cancer SMAD medicine.disease_cause tumor associated neutrophils 03 medical and health sciences 0302 clinical medicine medicine skin and connective tissue diseases Anti-TGF-β Protein kinase B PI3K/AKT/mTOR pathway Tumor microenvironment polarization integumentary system Chemistry technology industry and agriculture 030104 developmental biology Oncology Apoptosis 030220 oncology & carcinogenesis Cancer research Signal transduction Carcinogenesis human activities Transforming growth factor Research Paper |
| Zdroj: | Journal of Cancer |
| ISSN: | 1837-9664 |
| Popis: | Tumor associated neutrophils (TANs) play important roles in the progress of CRC. Since tumor microenvironments could influence the phenotypes of TANs, altering the tumor microenvironment to polarize the phenotype of TANs may be a new strategy for tumor treatment. This study aims to investigate the effect of anti-TGF-β on the polarization of TANs from a pro-tumor phenotype towards an anti-tumor phenotype in CRC. In this work, CRC patients had more infiltration of TANs and higher expression of TGF-β in CRC tissue when compared with the controls. In vitro, SW480 cells were co-cultured with primed neutrophils, which simulated the TANs in the tumor microenvironment, and TGF-β was blocked by anti-TGF-β (1D11) in order to polarize TANs. Anti-TGF-β treatment increased the cytotoxicity of TANs and decreased the metastatic chemoattractants secreted by TANs, and ultimately increased the apoptosis of CRC cells significantly while remarkably suppressing the migration of tumor cells. The changes of signaling pathways in the TANs and tumor cells were explored. The results showed that anti-TGF-β attenuated CRC may be partly mediated by suppression of PI3K/AKT signaling pathways in TANs and partly mediated by suppression of TGF-β/Smad signaling pathways in tumor cells. Furthermore, the tumor in the mice treated with 1D11 was obviously smaller and had reverse tumorigenesis compared with the controls, while neutrophil depletion reduced the anti-tumor effect of 1D11. Our data suggest that anti-TGF-β attenuates tumor growth via the polarization of TANs to an anti-tumor phenotype in CRC, which provides new strategies for CRC treatment. |
| Databáze: | OpenAIRE |
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