Activated macrophages are crucial during acute PM2.5 exposure-induced angiogenesis in lung cancer

Activated macrophages are crucial during acute PM2.5 exposure-induced angiogenesis in lung cancer
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活化的巨噬细胞在急性 PM2.5 暴露诱导的肺癌血管生成过程中至关重要

DOI:
10.3892/ol.2019.11133
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发表时间:
2019-11
期刊:
Oncol. Lett.
影响因子:
--
通讯作者:
JIANGE ZHANG
JIANGE ZHANG
中科院分区:
其他
文献类型:
--
作者:
RUYI LI;LIUQING YANG;NAN JIANG;FEIYUN WANG;PEI ZHANG;RUI ZHOU;JIANGE ZHANG

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环境颗粒物(PM2.5)在肺癌进展中的重要性已经得到了很好的证实;然而,PM2.5调节肺癌发展的确切机制尚未确定。目前的研究表明,增加血管内皮生长因子的mRNA和蛋白质表达水平在PM2.5诱导的巨噬细胞。然而,在刘易斯肺癌(LLC)细胞系中,急性PM2.5暴露后,血管生成细胞因子(血管内皮生长因子A、基质金属肽酶9、碱性成纤维细胞生长因子和血小板源性生长因子)的表达水平未发生显著变化。在LLC细胞急性暴露于PM2.5诱导的巨噬细胞上清液后,PM2.5诱导的活化巨噬细胞被揭示为上调血管生成细胞因子表达。在体内,通过建立聚乙烯醇海绵植入小鼠模型,支持PM2.5的促血管生成和巨噬细胞聚集功能。此外,PM2.5被证明可以增加皮下注射LLC的小鼠的血管生成和巨噬细胞募集。这些结果表明,PM2.5增加血管生成,巨噬细胞是PM2.5诱导的肺癌血管生成的关键介质。这些发现可能为肺癌治疗策略的发展提供新的见解。
The importance of ambient particulate matter (PM2.5) in lung cancer progression is well established; however, the precise mechanisms by which PM2.5 modulates lung cancer development have not yet been determined. The present study demonstrated increased mRNA and protein expression levels of vascular endothelial growth factor in PM2.5-induced macrophages. However, no significant changes to the expression levels of angiogenic cytokines (vascular endothelial growth factor A, matric metallopeptidase 9, basic fibroblast growth factor and platelet-derived growth factor) were observed in the Lewis lung carcinoma (LLC) cell line in response to acute PM2.5 exposure. PM2.5-induced activated macrophages were revealed to upregulate angiogenic cytokine expression following the acute exposure of LLC cells to PM2.5-induced macrophage supernatant. In vivo, the pro-angiogenic and macrophage accumulation functions of PM2.5 were supported by the establishment of a polyvinyl alcohol sponge implantation mouse model. Furthermore, PM2.5 was demonstrated to increase angiogenesis and macrophage recruitment in mice that were subcutaneously injected with LLCs. These results indicated that PM2.5 increases angiogenesis, and macrophages are crucial mediators of PM2.5-induced angiogenesis in lung cancer. These findings may provide novel insights for the development of lung cancer treatment strategies.
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