Alteration of cellular behavior and response to PI3K pathway inhibition by culture in 3D collagen gels.
Alteration of cellular behavior and response to PI3K pathway inhibition by culture in 3D collagen gels.
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DOI：
10.1371/journal.pone.0048024
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Zaman M
中科院分区：
文献类型：
--
作者：
Fallica B;Maffei JS;Villa S;Makin G;Zaman M
大多数对癌细胞药物反应的研究都是在平面(2D)组织培养塑料上培养的细胞进行的。新出现的研究表明，三维(3D)细胞外基质(ECM)的存在对正常的细胞行为至关重要，包括迁移、黏附、信号传递、增殖和凋亡。在这项研究中，我们研究了2D培养和3D ECM中癌细胞信号的差异，使用实时、活细胞跟踪来直接观察U2OS人骨肉瘤和MCF7人乳腺癌细胞嵌入1型胶原凝胶中。研究了重要的PI3K信号通路在不同生长条件下的激活情况，以及PI103对PI3K和mTOR抑制的反应。在3D凝胶中生长的细胞与在2D中生长的细胞相比，表现出增殖和迁移减少以及PI3K途径激活减少。我们的结果定量地证明了胶原ECM可以保护U2OS细胞免受PI103的影响。总体而言，我们的数据表明，与2D单层相比，3D凝胶可能为抗癌药物的研究提供了更好的介质，因此可以更好地了解细胞在类似自然环境中的反应和行为。
Most investigations into cancer cell drug response are performed with cells cultured on flat (2D) tissue culture plastic. Emerging research has shown that the presence of a three-dimensional (3D) extracellular matrix (ECM) is critical for normal cell behavior including migration, adhesion, signaling, proliferation and apoptosis. In this study we investigate differences between cancer cell signaling in 2D culture and a 3D ECM, employing real-time, live cell tracking to directly observe U2OS human osteosarcoma and MCF7 human breast cancer cells embedded in type 1 collagen gels. The activation of the important PI3K signaling pathway under these different growth conditions is studied, and the response to inhibition of both PI3K and mTOR with PI103 investigated. Cells grown in 3D gels show reduced proliferation and migration as well as reduced PI3K pathway activation when compared to cells grown in 2D. Our results quantitatively demonstrate that a collagen ECM can protect U2OS cells from PI103. Overall, our data suggests that 3D gels may provide a better medium for investigation of anti-cancer drugs than 2D monolayers, therefore allowing better understanding of cellular response and behavior in native like environments.
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影响因子：
3.8
作者：
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通讯作者：
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作者：
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