Strategy of STAT3β cell-specific expression in macrophages exhibits antitumor effects on mouse breast cancer
Strategy of STAT3β cell-specific expression in macrophages exhibits antitumor effects on mouse breast cancer
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DOI：
10.1038/gt.2015.70
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发表时间：
2015-12-01
期刊：
影响因子：
5.1
通讯作者：
Chen, T.
中科院分区：
文献类型：
--
作者：
Dang, W.;Tang, H.;Chen, T.
最近的研究强调了肿瘤相关巨噬细胞(TAMs)和肿瘤细胞之间的串扰在癌症进展和转移中的重要性。在我们的研究中，重组腺病毒AdCD68STAT3β被用来抑制TAMs中的STAT3及其下游信号通路。结果表明，CD68巨噬细胞特异性启动子控制下的STAT3β基因仅在巨噬细胞中表达，与4T1细胞共培养时可显著抑制乳腺癌细胞的运动和侵袭能力。此外，TAMS中细胞特异性STAT3β的表达通过调节肿瘤细胞与TAMS之间的串扰，延长了荷瘤小鼠的生存时间，并抑制了乳腺癌的生长、血管生成和转移。因此，我们的研究为STAT3β的抗肿瘤作用提供了一种新的策略。
Recent studies underscore the importance of crosstalk between tumor-associated macrophages (TAMs) and tumor cells in cancer progression and metastasis. In our study, AdCD68STAT3 beta, a recombinant adenovirus containing a STAT3 beta gene driven by CD68 macrophage-specific promoter, was used to suppress STAT3 and the downstream signaling pathways in TAMs. The results showed that STAT3 beta 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 STAT3 beta 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 STAT3 beta.