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云南锡矿尘诱导肺上皮细胞转化和成纤维细胞激活及其相互作用。

Induction of lung epithelial cell transformation and fibroblast activation by Yunnan tin mine dust and their interaction.

机构信息

Department of Pathology, The First Affiliated Hospital of Kunming Medical College, 650032 Kunming, China.

出版信息

Med Oncol. 2011 Dec;28 Suppl 1:S560-9. doi: 10.1007/s12032-010-9655-4. Epub 2010 Aug 18.

Abstract

Tumor-stroma interactions play a significant role in tumor development and progression. Our study employed an in vitro co-culture model of epithelial cells and fibroblasts to investigate the mechanism of and interaction between lung epithelial cell transformation and fibroblast activation induced by Yunnan tin mine dust. Epithelial cell transformation was evaluated using concanavalin A agglutination and anchorage-independent growth assays, and fibroblast activation was assessed via immunohistochemistry. The TGF-β1/Smad pathway was monitored by Western blot analysis and ELISA. We found concanavalin A agglutination and anchorage-independent growth assays of dust-exposed epithelial cells were positive, dust-exposed fibroblasts expressed α-SMA, and during the mine dust-induced tumorigenesis, TGF-β1/Smad signaling pathway changed. In conclusion, Yunnan tin mine dust is able to induce the malignant transformation of bronchial epithelial cells and fibroblast activation. Epithelial cells are the main target of mine dust. Bronchial epithelial cell transformation and fibroblast activation are correlated and synergistic. Their interdependence is related to the TGF-β1/Smad signaling pathway.

摘要

肿瘤-基质相互作用在肿瘤的发生和发展中起着重要作用。本研究采用上皮细胞和成纤维细胞体外共培养模型,研究云南锡矿尘诱导的肺上皮细胞转化与成纤维细胞激活的机制及相互作用。采用刀豆蛋白 A 凝集和非锚定依赖性生长实验评价上皮细胞转化,免疫组化法评价成纤维细胞激活。通过 Western blot 分析和 ELISA 监测 TGF-β1/Smad 通路。结果发现,暴露于粉尘的上皮细胞的刀豆蛋白 A 凝集和非锚定依赖性生长实验呈阳性,暴露于粉尘的成纤维细胞表达α-SMA,在矿尘诱导的肿瘤发生过程中,TGF-β1/Smad 信号通路发生改变。结论:云南锡矿尘能够诱导支气管上皮细胞恶性转化和成纤维细胞激活。上皮细胞是矿尘的主要作用靶点。支气管上皮细胞转化与成纤维细胞激活相关且协同,它们的相互依存关系与 TGF-β1/Smad 信号通路有关。

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