Parylene peel-off arrays to probe the role of cell-cell interactions in tumour angiogenesis

Parylene peel-off arrays to probe the role of cell-cell interactions in tumour angiogenesis
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DOI:
10.1039/b908036h
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发表时间:
2009-01-01
影响因子:
2.5
通讯作者:
Fischbach, Claudia
Fischbach, Claudia
中科院分区:
生物学4区
文献类型:
--
作者:
Tan, Christine P.;Seo, Bo Ri;Fischbach, Claudia

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微环境条件影响肿瘤血管生成,但细胞间相互作用在调节肿瘤细胞血管生成能力中的作用尚不清楚。我们已经制作了一种剥离细胞培养阵列(PeelArray)芯片,用于在大阵列形式中时空控制肿瘤细胞之间的相互作用,并分析针对这些条件的血管生成因子分泌。PeelArray芯片由聚乙二醇(PEG)处理的玻璃盖片组成,覆盖有对二甲苯-C模板,该模板可以很容易地剥离,以选择性地形成生物分子和细胞的微图案。我们已经设计了PeelArray芯片,可以在指定表面积的纤维连接蛋白特征上重复沉积大量均匀的孤立单个细胞或孤立细胞团。我们已经利用这个微制培养系统来研究肿瘤细胞分泌血管生成因子的情况,在存在或不存在由微图案控制的细胞-细胞接触的情况下。我们的结果表明,细胞之间的相互作用在调节不同癌细胞系中血管生成因子(即血管内皮生长因子[VEGF]和白介素8[IL-8])的表达方面发挥了协同作用,而不受其他更复杂的微环境信号(如缺氧)的影响。我们的PeelArray芯片是一种简单且适应性强的微图案化方法,可以对蛋白质分泌进行定量分析,从而更好地了解细胞间相互作用调节肿瘤细胞行为和血管生成的机制。
Microenvironmental conditions impact tumour angiogenesis, but the role of cell-cell interactions in modulating the angiogenic capability of tumour cells is not well understood. We have microfabricated a peel-off cell-culture array (PeelArray) chip to spatiotemporally control interactions between tumour cells in a large array format and to analyse angiogenic factor secretion in response to these conditions. The PeelArray chip consists of a polyethylene glycol (PEG) treated glass coverslip coated with a parylene-C template that can be easily peeled off to selectively micropattern biomolecules and cells. We have designed the PeelArray chip to reproducibly deposit large uniform arrays of isolated single cells or isolated cell clusters on fibronectin features of defined surface areas. We have utilised this microfabricated culture system to study the secretion of angiogenic factors by tumour cells, in the presence or absence of cell-cell contact as controlled by micropatterning. Our results indicate that cell-cell interactions play a synergistic role in regulating the expression of angiogenic factors (i.e., vascular endothelial growth factor [VEGF] and interleukin-8 [IL-8]) in various cancer cell lines, independent of other more complex microenvironmental cues (e.g. hypoxia). Our PeelArray chip is a simple and adaptable micropatterning method that enables quantitative profiling of protein secretions and hence, a better understanding of the mechanisms by which cell-cell interactions regulate tumour cell behaviour and angiogenesis.