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Tumor necrosis factor receptor II (TNFR2) promotes the growth of mouse CT26 colon cancer
Chen, X; Li, P; Yang, X; Miao, X; Lou, H
2018-05-01
Source PublicationThe Journal of Immunology
Pages178.7-null
Publication PlaceFrederick
AbstractTNFR2 is expressed by several tumor cells including colon cancer, Hodgkin lymphoma, myeloma, renal carcinoma and ovarian cancer. Recently, TNFR2 is becoming appreciated as an oncogene. However, the exact role of TNFR2 on the tumor development remains to be fully understood. In this study, we examined the tumorigenesis and growth of mouse CT26 colon cancer cell lines with genetically modified TNFR2 expression in syngeneic Balb/c mice. We used CRISPR/Cas9- induced loss-of-function approaches to obtain stable TNFR2 KO CT26 cell line and gain-of-function techniques to obtain TNFR2 overexpression CT26 cell line. WT, TNFR2 KO and TNFR2 overexpressing CT26 cells were inoculated s.c. into the mice. Although TNFR2 overexpressing CT26 tumor grew markedly faster than TNFR2 KO CT26 cells, there was no difference in the initial tumorigenesis, Intriguingly, all TNFR2 KO CT26 tumors completely regressed 2 weeks after inoculation. The proportion of Foxp3+ Tregs, as well as their TNFR2 expression, in draining LNs was markedly higher in mice bearing TNFR2 overexpressing CT26 tumor. The levels of soluble TNFR2 in the peripheral blood of CT26 tumor bearing mice were ~3 folds higher than that in tumor free mice, which is comparable with the elevated levels of soluble TNFR2 in human tumor patients. In mice bearing TNFR2 overexpressing CT26 tumors, the levels of soluble TNFR2 was >4 folds higher than that in mice bearing WT CT26 tumors. In vitro, exogenous TNF was able to upregulate TNFR2 surface expression on CT26 tumor cells. Taken together, our data suggest that TNF-TNFR2 signaling pathway may play a major role in tumor growth and tumor immune evasion, and thus may represent an important therapeutic target. [Supported by the University of Macau Research Grants (MYRG2016-00023-ICMS-QRCM, and MYRG2017-00120-ICMS) and a grant from the Science and Technology Development Fund (FDCT); Macao S.A.R. (014/2015/A1)]
KeywordTNFR2 CT26 cancer knockout
URLView the original
Language英語English
The Source to ArticlePB_Publication
PUB ID40796
Document TypeConference paper
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorChen, X
Recommended Citation
GB/T 7714
Chen, X,Li, P,Yang, X,et al. Tumor necrosis factor receptor II (TNFR2) promotes the growth of mouse CT26 colon cancer[C], Frederick, 2018, 178.7-null.
APA Chen, X., Li, P., Yang, X., Miao, X., & Lou, H (2018). Tumor necrosis factor receptor II (TNFR2) promotes the growth of mouse CT26 colon cancer. The Journal of Immunology, 178.7-null.
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