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Strategy of STAT3β cell-specific expression in macrophages exhibits antitumor effects on mouse breast cancer

Abstract

Recent studies underscore the importance of crosstalk between tumor-associated macrophages (TAMs) and tumor cells in cancer progression and metastasis. In our study, AdCD68STAT3β, a recombinant adenovirus containing a STAT3β gene driven by CD68 macrophage-specific promoter, was used to suppress STAT3 and the downstream signaling pathways in TAMs. The results showed that STAT3β gene under the control of CD68 macrophage-specific promoter was only expressed in macrophages, which significantly inhibited the motility and invasion of breast cancer cells when co-cultured with 4T1 cells. Moreover, cell-specific STAT3β expression in TAMs extended survival of tumor-bearing mice and suppressed breast tumor growth, angiogenesis and metastasis, by regulating the crosstalk between tumor cells and TAMs. Therefore, our study provided a novel strategy for the antitumor effects of STAT3β.

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Acknowledgements

We thank Dr Yang'an Wen (First Affiliated Hospital, Chongqing Medical University, Chongqing, China) for technical supporting; Dr Tong-Chuan He (University of Chicago Medical Center, Chicago, IL, USA) for providing adenovirus AdEasy system; and Dr Ping Li and Dr Yao Hai for assisting with animal experiments. This work was supported by the National Natural Science Foundation of China (No. 81272544).

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Correspondence to T Chen.

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Dang, W., Tang, H., Cao, H. et al. Strategy of STAT3β cell-specific expression in macrophages exhibits antitumor effects on mouse breast cancer. Gene Ther 22, 977–983 (2015). https://doi.org/10.1038/gt.2015.70

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