Anti-TGF-β attenuates tumor growth via polarization of tumor associated neutrophils towards an anti-tumor phenotype in colorectal cancer

Qin, Fengxian; Liu, Xiaoyong; Chen, Jifei; Huang, Shishun; Wei, Wei; Zou, Yan; Liu, Xuexiang; Deng, Kaifeng; Mo, Shanying; Chen, Jianming; Chen, Xiaoli; Huang, Yujie; Liang, Weijun

doi:10.7150/jca.38179

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International Journal of Biological Sciences

International Journal of Medical Sciences

Theranostics

Journal of Genomics

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J Cancer 2020; 11(9):2580-2592. doi:10.7150/jca.38179 This issue Cite

Research Paper

Anti-TGF-β attenuates tumor growth via polarization of tumor associated neutrophils towards an anti-tumor phenotype in colorectal cancer

Fengxian Qin^1*✉, Xiaoyong Liu^2*, Jifei Chen^1*, Shishun Huang¹, Wei Wei¹, Yan Zou¹, Xuexiang Liu¹, Kaifeng Deng¹, Shanying Mo¹, Jianming Chen¹, Xiaoli Chen¹, Yujie Huang¹, Weijun Liang^1✉

1. Medical Science Laboratory, the Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, P. R. China 545005
2. Department of Clinical Laboratory, Liuzhou Municipal Liutie Center Hospital, Liuzhou, Guangxi, P. R. China 545007
* The authors contributed equally to this work.

Citation:

Qin F, Liu X, Chen J, Huang S, Wei W, Zou Y, Liu X, Deng K, Mo S, Chen J, Chen X, Huang Y, Liang W. Anti-TGF-β attenuates tumor growth via polarization of tumor associated neutrophils towards an anti-tumor phenotype in colorectal cancer. J Cancer 2020; 11(9):2580-2592. doi:10.7150/jca.38179. https://www.jcancer.org/v11p2580.htm

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Abstract

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.

Keywords: tumor associated neutrophils, colorectal cancer, Anti-TGF-β, polarization, phenotype

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APA

Qin, F., Liu, X., Chen, J., Huang, S., Wei, W., Zou, Y., Liu, X., Deng, K., Mo, S., Chen, J., Chen, X., Huang, Y., Liang, W. (2020). Anti-TGF-β attenuates tumor growth via polarization of tumor associated neutrophils towards an anti-tumor phenotype in colorectal cancer. Journal of Cancer, 11(9), 2580-2592. https://doi.org/10.7150/jca.38179.

ACS

Qin, F.; Liu, X.; Chen, J.; Huang, S.; Wei, W.; Zou, Y.; Liu, X.; Deng, K.; Mo, S.; Chen, J.; Chen, X.; Huang, Y.; Liang, W. Anti-TGF-β attenuates tumor growth via polarization of tumor associated neutrophils towards an anti-tumor phenotype in colorectal cancer. J. Cancer 2020, 11 (9), 2580-2592. DOI: 10.7150/jca.38179.

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CSE

Qin F, Liu X, Chen J, Huang S, Wei W, Zou Y, Liu X, Deng K, Mo S, Chen J, Chen X, Huang Y, Liang W. 2020. Anti-TGF-β attenuates tumor growth via polarization of tumor associated neutrophils towards an anti-tumor phenotype in colorectal cancer. J Cancer. 11(9):2580-2592.

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