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Updated: Aug 6, 2025
Isolation of Circulating Tumor Cells in an Orthotopic Mouse Model of Colorectal Cancer
Published on: July 18, 2017
TNFR2 deficiency impairs the growth of mouse colon cancer
Ping Li1, Yang Yang1, Xinyu Yang1
1State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Science, University of Macau, Macau SAR, 999078, P.R. China.
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.
Insights
Tumor necrosis factor receptor type II (TNFR2) deficiency impaired colon cancer cell growth in vitro and in vivo. This suggests TNFR2 antagonism could be a viable cancer treatment strategy.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Tumor necrosis factor receptor type II (TNFR2) is present on various cancer cells, but its role in tumor progression is not fully understood.
- TNFR2 expression is observed in colon cancer, non-Hodgkin lymphoma, myeloma, renal carcinoma, and ovarian cancer.
Purpose of the Study:
- To investigate the impact of TNFR2 genetic ablation on the in vitro and in vivo growth of mouse colon cancer cells (MC38 and CT26).
- To explore the underlying mechanisms by which TNFR2 influences cancer cell proliferation and tumor development.
Main Methods:
- CRISPR/Cas9 technology was employed to create TNFR2-deficient MC38 and CT26 colon cancer cell lines.
- In vitro assays assessed cell proliferation and colony formation. In vivo studies evaluated tumor growth in mice and characterized tumor-infiltrating CD8 T cells.
Main Results:
- TNFR2 deficiency significantly reduced cancer cell proliferation and colony formation in vitro.
- This was linked to inhibited AKT phosphorylation and increased autophagy-mediated cell death.
- In vivo, TNFR2-deficient tumors showed impaired growth, reduced soluble TNFR2 levels, and increased intratumoral CD8+ T cells.
Conclusions:
- TNFR2 plays a critical role in the growth of mouse colon cancers.
- Targeting TNFR2 may represent a promising therapeutic strategy for cancer treatment.
