Engineering cancer microenvironments for in vitro 3-D tumor models.
Engineering cancer microenvironments for in vitro 3-D tumor models.
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DOI：
10.1016/j.mattod.2015.05.002
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发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
Demirci U
中科院分区：
文献类型：
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作者：
Asghar W;El Assal R;Shafiee H;Pitteri S;Paulmurugan R;Demirci U
肿瘤的自然微环境由细胞外基质(ECM)、血管系统和支持基质细胞组成。细胞外基质的物理特性以及细胞成分在控制癌细胞的增殖、凋亡、代谢和分化方面起着至关重要的作用。为了模拟人体外的肿瘤微环境进行药物测试，通常使用二维(2-D)和小鼠肿瘤模型。尽管这些常规方法被用于临床前研究，但它们仍然存在挑战。例如，小鼠肿瘤模型昂贵，难以用于常规药物筛选。另一方面，2-D体外模型操作简单，但它们不能概括自然的肿瘤微环境，因为它们不能捕捉重要的三维(3-D)细胞-细胞、细胞-基质信号通路以及肿瘤微环境的多细胞异质成分，如基质细胞和免疫细胞。三维(3-D)体外肿瘤模型旨在接近模拟癌症微环境，并已成为常规药物筛选方法的替代方法。在这里，我们回顾了在三维肿瘤模型生成方面的最新进展，并强调了未来在药物测试中的应用方向。
The natural microenvironment of tumors is composed of extracellular matrix (ECM), blood vasculature, and supporting stromal cells. The physical characteristics of ECM as well as the cellular components play a vital role in controlling cancer cell proliferation, apoptosis, metabolism, and differentiation. To mimic the tumor microenvironment outside the human body for drug testing, two-dimensional (2-D) and murine tumor models are routinely used. Although these conventional approaches are employed in preclinical studies, they still present challenges. For example, murine tumor models are expensive and difficult to adopt for routine drug screening. On the other hand, 2-D in vitro models are simple to perform, but they do not recapitulate natural tumor microenvironment, because they do not capture important three-dimensional (3-D) cell–cell, cell–matrix signaling pathways, and multi-cellular heterogeneous components of the tumor microenvironment such as stromal and immune cells. The three-dimensional (3-D) in vitro tumor models aim to closely mimic cancer microenvironments and have emerged as an alternative to routinely used methods for drug screening. Herein, we review recent advances in 3-D tumor model generation and highlight directions for future applications in drug testing.