Three-dimensional in vitro tumor models for cancer research and drug evaluation.
Three-dimensional in vitro tumor models for cancer research and drug evaluation.
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DOI：
10.1016/j.biotechadv.2014.07.009
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发表时间：
2014-11-15
影响因子：
16
通讯作者：
Jia, Xinqiao
中科院分区：
文献类型：
--
作者：
Xu, Xian;Farach-Carson, Mary C.;Jia, Xinqiao
关键词：
当细胞获得基因组不稳定和炎症，产生异常水平的表观遗传因子/蛋白质和肿瘤抑制因子，重编程能量代谢和逃避免疫破坏，导致细胞周期/正常生长中断时，癌症就发生了。癌变的早期事件是极性丧失和脱离天然基底膜，使细胞形成不同的三维（3D）结构，相互作用并与周围的微环境相互作用。尽管从传统的体外研究中积累了有价值的信息，其中细胞在平坦和坚硬的塑料表面上生长（2D培养），但这种培养条件并不能反映肿瘤组织的基本特征。此外，对癌症转移的基本理解不能轻易地从二维研究中获得，因为它们缺乏在癌症转移过程中发生的复杂和动态的细胞-细胞通信和细胞-基质相互作用。这些缺点，加上缺乏空间深度和细胞连通性，限制了二维培养在准确检测游离或隔离在纳米颗粒中的药理活性化合物方面的适用性。为了概括天然肿瘤微环境的特征，各种仿生3D肿瘤模型已经被开发出来，将癌症和基质细胞、相关基质成分、生化和生物物理线索纳入一个时空集成的系统。在本文中，我们回顾了利用组织工程原理创建三维肿瘤模型的最新进展。然后，我们评估了这些新型模型在抗癌药物及其输送系统测试中的效用。我们强调了3D体外肿瘤和传统单层培养反应的深刻差异。总体而言，生物学原理和工程方法的战略性整合将提高对肿瘤进展和侵袭的理解，并支持为癌症患者发现更个性化的一线治疗方法。
Cancer occurs when cells acquire genomic instability and inflammation, produce abnormal levels of epigenetic factors/proteins and tumor suppressors, reprogram the energy metabolism and evade immune destruction, leading to the disruption of cell cycle/normal growth. An early event in carcinogenesis is loss of polarity and detachment from the natural basement membrane, allowing cells to form distinct three-dimensional (3D) structures that interact with each other and with the surrounding microenvironment. Although valuable information has been accumulated from traditional in vitro studies in which cells are grown on flat and hard plastic surfaces (2D culture), this culture condition does not reflect the essential features of tumor tissues. Further, fundamental understanding of cancer metastasis cannot be obtained readily from 2D studies because they lack the complex and dynamic cell-cell communications and cell-matrix interactions that occur during cancer metastasis. These shortcomings, along with lack of spatial depth and cell connectivity, limit the applicability of 2D cultures to accurate testing of pharmacologically active compounds, free or sequestered in nanoparticles. To recapitulate features of native tumor microenvironments, various biomimetic 3D tumor models have been developed to incorporate cancer and stromal cells, relevant matrix components, and biochemical and biophysical cues, into one spatially and temporally integrated system. In this article, we review recent advances in creating 3D tumor models employing tissue engineering principles. We then evaluate the utilities of these novel models for the testing of anticancer drugs and their delivery systems. We highlight the profound differences in responses from 3D in vitro tumors and conventional monolayer cultures. Overall, strategic integration of biological principles and engineering approaches will both improve understanding of tumor progression and invasion and support discovery of more personalized first line treatments for cancer patients.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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Rylander, Marissa Nichole
DOI：
10.1146/annurev-bioeng-071910-124729
发表时间：
2011-08-15
影响因子：
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作者：
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通讯作者：
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