TGF-β secreted by tumor-associated macrophages promotes proliferation and invasion of colorectal cancer via miR-34a-VEGF axis (Retracted article. See JAN, 2023)
TGF-β secreted by tumor-associated macrophages promotes proliferation and invasion of colorectal cancer via miR-34a-VEGF axis (Retracted article. See JAN, 2023)
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肿瘤相关巨噬细胞分泌的TGF-β通过miR-34a-VEGF轴促进结直肠癌的增殖和侵袭。
DOI：
10.1080/15384101.2018.1556064
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发表时间：
2018-12-17
期刊：
影响因子：
4.3
通讯作者：
Zhao, Hongchao
中科院分区：
文献类型：
--
作者：
Zhang, Danhua;Qiu, Xinguang;Zhao, Hongchao
据报道，肿瘤相关巨噬细胞（TAM）参与结直肠癌（CRC）的进展。然而，其在CRC中的生物学作用和潜在机制仍有待阐明。本研究采用免疫组化方法检测巨噬细胞标志物CD 68和转化生长因子β 1（TGF-β 1）在结直肠癌组织及癌旁组织中的表达。采用实时定量PCR（qRT-PCR）和western blot检测CRC肿瘤组织和外周血巨噬细胞中miR-34 a、TGF-β 1和血管内皮生长因子（VEGF）的表达水平。ELISA法检测培养上清中TGF-β 1水平。MTT法和Transwell法分别检测细胞增殖和侵袭能力。结果显示，在结直肠癌组织和外周血巨噬细胞中，miR-34 a表达下调，TGF-β 1和VEGF表达上调。TAM分泌的TGF-β 1促进了CRC细胞的增殖和侵袭。TGF-β 1介导的miR-34 a下调通过上调VEGF促进CRC细胞的增殖和侵袭。miR-34 a通过抑制VEGF表达在体内发挥CRC中的抗肿瘤作用。结论TAMs分泌的TGF-β 1通过调节miR-34 a/VEGF轴促进结直肠癌的增殖和侵袭。
Tumor-associated macrophages (TAMs) were reported to be involved in colorectal cancer (CRC) progression. However, its biological role and underlying mechanism in CRC remained to be elucidated. In this study, the expressions of the macrophage marker CD68 and transforming growth factor beta 1 (TGF-beta 1) in CRC tumor tissues and adjacent tissues were detected by immunohistochemistry. The expression levels of miR-34a, TGF-beta 1 and vascular endothelial growth factor (VEGF) in CRC tumor tissues and peripheral blood macrophages were measured by quantitative real-time PCR (qRT-PCR) and western blot. TGF-beta 1 levels in culture supernatant were detected by ELISA. The cell proliferation and invasion of human CRC cell lines CL187 and HCT116 were determined by MTT assay and Transwell assay, respectively. The results showed that the expression of miR-34a was downregulated whereas TGF-beta 1 and VEGF were upregulated in CRC tumor tissues and peripheral blood macrophages. TGF-beta 1 secreted by TAMs promoted the proliferation and invasion of CRC cells. TGF-beta 1-mediated miR-34a downregulation contributed to the proliferation and invasion of CRC cells via upregulating VEGF. MiR-34a in vivo exerted anti-tumor effect in CRC via inhibiting VEGF expression. In conclusion, TGF-beta 1 secreted by TAMs promoted CRC proliferation and invasion through regulating miR-34a/VEGF axis.