Quantitative phase imaging reveals matrix stiffness-dependent growth and migration of cancer cells

Quantitative phase imaging reveals matrix stiffness-dependent growth and migration of cancer cells
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DOI:
10.1038/s41598-018-36551-5
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发表时间:
2019-01-22
期刊:
影响因子:
4.6
通讯作者:
Popescu, Gabriel
Popescu, Gabriel
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li, Yanfen;Fanous, Michael J.;Popescu, Gabriel

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癌症进展涉及肿瘤微环境中协调增殖和侵袭过程的复杂信号。细胞外基质(ECM)在这种微环境中的机械特性已被证明影响生长和迁移表型,入侵之前。在这里,我们提出了一个无标记的定量相位成像技术,空间光干涉显微镜(SLIM)的整合-与蛋白质结合的水凝胶基板-探索ECM的刚度如何影响黑色素瘤细胞的不同转移潜力。相对于低转移潜能的细胞,高转移潜能的黑素瘤细胞表现出增加的生长和速度特征。在高转移性人群中的细胞速度显示出对基质硬度的相对不敏感性,这表明采用独立于力学的迁移例程以促进侵袭。SLIM和工程基板的使用提供了一种新的方法来表征作为微环境参数的函数的活细胞的侵入性。这项工作提供了对生长,迁移和转移潜力之间关系的基本见解,并为分析癌细胞的临床分级和患者特异性治疗方案的开发提供了新的工具。
Cancer progression involves complex signals within the tumor microenvironment that orchestrate proliferation and invasive processes. The mechanical properties of the extracellular matrix (ECM) within this microenvironment has been demonstrated to influence growth and the migratory phenotype that precedes invasion. Here we present the integration of a label-free quantitative phase imaging technique, spatial light interference microscopy (SLIM)-with protein-conjugated hydrogel substrates-to explore how the stiffness of the ECM influences melanoma cells of varying metastatic potential. Melanoma cells of high metastatic potential demonstrate increased growth and velocity characteristics relative to cells of low metastatic potential. Cell velocity in the highly metastatic population shows a relative insensitivity to matrix stiffness suggesting adoption of migratory routines that are independent of mechanics to facilitate invasion. The use of SLIM and engineered substrates provides a new approach to characterize the invasive properties of live cells as a function of microenvironment parameters. This work provides fundamental insight into the relationship between growth, migration and metastatic potential, and provides a new tool for profiling cancer cells for clinical grading and development of patient-specific therapeutic regimens.