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首页> 美国卫生研究院文献>British Journal of Cancer >Paracrine control of differentiation in the alveolar carcinoma A549 by human foetal lung fibroblasts.
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Paracrine control of differentiation in the alveolar carcinoma A549 by human foetal lung fibroblasts.

机译：人胎肺成纤维细胞对肺泡癌A549中旁分泌的分化控制。

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摘要

Synthesis of pulmonary surfactant (PS) is necessary for normal functioning of the lungs and its production is indicative of normal differentiated lung. The human alveolar carcinoma, A549, has been found to synthesis and secrete PS in vitro. The purpose of this study was to optimise the culture conditions for PS synthesis by A549 as well as to determine the potential role of foetal lung fibroblasts in the induction of PS by glucocorticoids. A549 cells growing in filter wells produced higher levels of PS in response to steroid, a 5-fold increase on the filter well compared to only a 1.5-fold increase when the cells were cultured on a conventional plastic substrate. A549 cells grown in filter wells responded to coculture with fibroblasts whether in direct contact or separated co-culture. A 20-fold increase in PS over control values was observed in separated steroid-treated co-cultures, suggesting the presence of a diffusible factor. A partially purified factor was isolated from fibroblast conditioned medium which was capable of inducing differentiation and other phenotypic changes in A549, namely induction of PS, reduction of plasminogen activator activity and reduction in the in vivo growth of A549 xenografts in nude mice. These results suggest that, under the correct conditions, A549 cells, although transformed, still retain the capacity to respond to differentiation-inducing signals from normal fibroblasts.
机译：肺表面活性剂（PS）的合成对于肺的正常功能是必需的，并且其产生表明肺正常分化。已发现人类肺泡癌A549在体外合成并分泌PS。这项研究的目的是优化A549合成PS的培养条件，并确定胎儿肺成纤维细胞在糖皮质激素诱导PS中的潜在作用。在过滤孔中生长的A549细胞响应类固醇产生更高水平的PS，在过滤孔中增加了5倍，而在常规塑料基材上培养细胞时，其仅增加了1.5倍。过滤孔中生长的A549细胞对成纤维细胞的共培养有反应，无论是直接接触还是分开共培养。在单独的类固醇处理的共培养物中观察到PS较对照值增加了20倍，表明存在扩散因子。从成纤维细胞条件培养基中分离出部分纯化的因子，其能够诱导A549的分化和其他表型改变，即诱导PS，降低纤溶酶原激活物活性以及降低A549异种移植物在裸鼠体内的生长。这些结果表明，在正确的条件下，A549细胞尽管已转化，但仍保留了对来自正常成纤维细胞的分化诱导信号作出反应的能力。

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