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化疗处理后的癌细胞系上清液可以改变血管生成。

Supernatants derived from chemotherapy-treated cancer cell lines can modify angiogenesis.

机构信息

Department of Oncology, Division of Clinical Sciences, St George's, University of London, London SW17 0RE, UK.

出版信息

Br J Cancer. 2012 Feb 28;106(5):896-903. doi: 10.1038/bjc.2012.13. Epub 2012 Jan 31.

Abstract

BACKGROUND

There is evidence that tumours produce substances such as cytokines and microvesicular bodies bearing bioactive molecules, which support the carcinogenic process. Furthermore, chemotherapy has also been shown to modify these exudates and in doing so, neutralise their tumourigenic influence.

METHODS

In the current study, we have investigated the effect of chemotherapy agents on modifying the cytokine profile and microvesicular cargo of supernatants derived from cancer cell lines. In addition, we have explored the effect of these tumour-derived supernatants on angiogenesis, and how chemotherapy can alter the supernatants rendering them less pro-angiogenic.

RESULTS

Herein, we show that supernatants contain a rich cocktail of cytokines, a number of which are potent modulators of angiogenesis. They also contain microvesicular bodies containing RNA transcripts that code for proteins involved in transcription, immune modulation and angiogenesis. These supernatants altered intracellular signalling molecules in endothelial cells and significantly enhanced their tubulogenic character; however, this was severely compromised when supernatants from tumours treated with chemotherapy was used instead.

CONCLUSION

This study suggests tumour exudates and bioactive material from tumours can influence cellular functions, and that treatment with some chemotherapy can serve to negate these pro-tumourigenic processes.

摘要

背景

有证据表明肿瘤会产生一些物质,如细胞因子和携带生物活性分子的微泡体,这些物质支持致癌过程。此外,化疗也已被证明可以改变这些渗出物,从而中和其致瘤影响。

方法

在目前的研究中,我们研究了化疗药物对改变癌细胞系上清液中细胞因子谱和微泡货物的影响。此外,我们还探讨了这些肿瘤来源的上清液对血管生成的影响,以及化疗如何改变上清液使其减少促血管生成作用。

结果

本文显示,上清液中含有丰富的细胞因子混合物,其中一些是血管生成的有效调节剂。它们还含有含有编码参与转录、免疫调节和血管生成的蛋白质的 RNA 转录本的微泡体。这些上清液改变了内皮细胞内的信号分子,并显著增强了它们的管状形成特征;然而,当使用经化疗处理的肿瘤的上清液时,这种情况严重受损。

结论

本研究表明,肿瘤渗出物和肿瘤中的生物活性物质可以影响细胞功能,而某些化疗的治疗可以消除这些促肿瘤生成过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1a/3305950/057faa42783f/bjc201213f1.jpg

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