3D In Vitro Models for Investigating the Role of Stiffness in Cancer Invasion.

3D In Vitro Models for Investigating the Role of Stiffness in Cancer Invasion.
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3D体外模型,用于研究僵硬在癌症侵袭中的作用。

DOI:
10.1021/acsbiomaterials.0c01530
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发表时间:
2023-07-10
影响因子:
5.8
通讯作者:
Cheema, Umber
Cheema, Umber
中科院分区:
工程技术2区
文献类型:
--
作者:
Micalet, Auxtine;Moeendarbary, Emad;Cheema, Umber

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背景资料:肿瘤发生归因于癌细胞通过生物化学线索和物理刺激与肿瘤微环境的相互作用。增加的基质沉积和胶原纤维的重新排列被癌细胞检测到,诱导上皮细胞向间充质细胞的转化,这反过来刺激细胞运动性和侵袭性。方法:本文综述了物理微环境在癌症侵袭中的作用的研究现状。这是通过使用系统方法和提供荟萃分析实现的。特别关注的是上皮癌的体外三维模型。我们研究了诸如基质硬化的影响、基质细胞的激活等问题,并确定了基于机械疗法的潜在进展。结果:荟萃分析显示,64%的研究报告随着硬度增加,癌症侵袭促进,而36%的研究报告相反。实验方法和数据解释各不相同,每种方法对癌症侵袭的影响都不同。例如,使用的实验时间范围(24小时至21天)、使用的聚合物类型(24种类型)和细胞系的选择(33种细胞系)。3D矩阵的刚度在0.5至300 kPa之间变化,这些矩阵的刚度中有19%超出了通常接受的生理范围。100%的生物硬度范围(高于20 kPa)以外的研究报告称,硬度不会促进癌症侵袭。结论:考虑到这一分析,我们告知可能是最相关的实验方法的类型,并提供什么是标准化的协议和报告策略。
Background: Tumorigenesis is attributed to the interactions of cancer cells with the tumor microenvironment through both biochemical cues and physical stimuli. Increased matrix deposition and realignment of the collagen fibers are detected by cancer cells, inducing epithelial-to-mesenchymal transition, which in turn stimulates cell motility and invasiveness. Methods: This review provides an overview of current research on the role of the physical microenvironment in cancer invasion. This was achieved by using a systematic approach and providing meta-analyses. Particular focus was placed on in vitro three-dimensional models of epithelial cancers. We investigated questions such as the effect of matrix stiffening, activation of stromal cells, and identified potential advances in mechano-based therapies. Results: Meta-analysis revealed that 64% of studies report cancer invasion promotion as stiffness increases, while 36% report the opposite. Experimental approaches and data interpretations were varied, each affecting the invasion of cancer differently. Examples are the experimental timeframes used (24 h to 21 days), the type of polymer used (24 types), and choice of cell line (33 cell lines). The stiffness of the 3D matrices varied from 0.5 to 300 kPa and 19% of these matrices’ stiffness were outside commonly accepted physiological range. 100% of the studies outside biological stiffness range (above 20 kPa) report that stiffness does not promote cancer invasion. Conclusions: Taking this analysis into account, we inform on the type of experimental approaches that could be the most relevant and provide what would be a standardized protocol and reporting strategy.
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