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Int J Biol Sci 2023; 19(4):1024-1035. doi:10.7150/ijbs.72606 This issue Cite

Research Paper

TNFR2 deficiency impairs the growth of mouse colon cancer

Ping Li1, Yang Yang1, Xinyu Yang1, Yifei Wang1, Chon-Kit Chou1, Mengmeng Jiang1, Jingbin Zheng1, Fengyang Chen1, Xin Chen1,2,3✉

1. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Science, University of Macau, Macau SAR, 999078, P.R. China.
2. Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Macau SAR, China.
3. MoE Frontiers Science Center for Precision Oncology, University of Macau, Macau SAR, China.

✉ Corresponding author: Xin Chen, E-mail: xchenedu.mo.

Citation:
Li P, Yang Y, Yang X, Wang Y, Chou CK, Jiang M, Zheng J, Chen F, Chen X. TNFR2 deficiency impairs the growth of mouse colon cancer. Int J Biol Sci 2023; 19(4):1024-1035. doi:10.7150/ijbs.72606. https://www.ijbs.com/v19p1024.htm
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Abstract

Graphic abstract

Objective: Tumor necrosis factor (TNF) receptor type II (TNFR2) is expressed by a wide spectrum of tumor cells including colon cancer, non-Hodgkin lymphoma, myeloma, renal carcinoma and ovarian cancer, and its exact role remains to be fully understood. In this study, we examined the effect of genetic ablation of TNFR2 on in vitro and in vivo growth of mouse MC38 and CT26 colon cancer cells.

Methods: CRISPR/Cas9 technology was used to knockout TNFR2 on mouse MC38 and CT26 colon cancer cells. In vitro growth and colony formation of wild-type (W.T.) and TNFR2 deficiency of MC38 and CT26 cells, as well as the potential mechanism, was studied. The growth of W.T. and TNFR2 deficient MC38 and CT26 tumors in mice and intratumoral CD8 CTLs were also examined.

Results: TNFR2 deficiency impaired in vitro proliferation and colony formation of cancer cells. This was associated with the inhibition of protein kinase B (AKT) phosphorylation and enhanced autophagy-induced cell death. Moreover, deficiency of TNFR2 also markedly impaired in vivo growth of MC38 or CT26 in the syngeneic C57BL/6 mice or BALB/c mice, respectively, accompanied by the decrease in soluble TNFR2 levels in the circulation and the increase in the number of tumor-infiltrating IFNγ+ CD8 cells.

Conclusion: TNFR2 plays a role in the growth of mouse colon cancers. Our study provides further experimental evidence to support the development of TNFR2 antagonistic agents in the treatment of cancer.

Keywords: Tumor necrosis factor (TNF), tumor necrosis factor receptor type II (TNFR2), colon cancer, cancer immunotherapy.

Citation styles

APA
Li, P., Yang, Y., Yang, X., Wang, Y., Chou, C.K., Jiang, M., Zheng, J., Chen, F., Chen, X. (2023). TNFR2 deficiency impairs the growth of mouse colon cancer. International Journal of Biological Sciences, 19(4), 1024-1035. https://doi.org/10.7150/ijbs.72606.

ACS
Li, P.; Yang, Y.; Yang, X.; Wang, Y.; Chou, C.K.; Jiang, M.; Zheng, J.; Chen, F.; Chen, X. TNFR2 deficiency impairs the growth of mouse colon cancer. Int. J. Biol. Sci. 2023, 19 (4), 1024-1035. DOI: 10.7150/ijbs.72606.

NLM
Li P, Yang Y, Yang X, Wang Y, Chou CK, Jiang M, Zheng J, Chen F, Chen X. TNFR2 deficiency impairs the growth of mouse colon cancer. Int J Biol Sci 2023; 19(4):1024-1035. doi:10.7150/ijbs.72606. https://www.ijbs.com/v19p1024.htm

CSE
Li P, Yang Y, Yang X, Wang Y, Chou CK, Jiang M, Zheng J, Chen F, Chen X. 2023. TNFR2 deficiency impairs the growth of mouse colon cancer. Int J Biol Sci. 19(4):1024-1035.

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