Interfacial geometry dictates cancer cell tumorigenicity
Interfacial geometry dictates cancer cell tumorigenicity
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DOI：
10.1038/nmat4610
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发表时间：
2016-08-01
期刊：
影响因子：
41.2
通讯作者：
Kilian, Kristopher A.
中科院分区：
文献类型：
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作者：
Lee, Junmin;Abdeen, Amr A.;Kilian, Kristopher A.
在肿瘤组织的异质结构中，存在一个难以捉摸的干细胞样细胞群体，其涉及复发和转移（1，2）。在这里，通过使用工程细胞外基质，我们表明，在肿瘤组织周边的几何特征将引发一个干细胞样表型的细胞群体。这些细胞在体外显示出癌症干细胞的特征，以及在原发性肿瘤生长和肺转移的小鼠模型中增强的致瘤性。我们还表明，界面的几何形状调节细胞的形状，通过整合素α（5）β（1），MAPK和STAT活性，并启动多能性信号的粘附。我们对几种人类癌细胞系的研究结果表明，界面几何形状触发了调节癌细胞状态的一般机制。类似于生长中的肿瘤如何选择正常的可溶性信号通路（3），我们的研究结果表明癌症也可以利用几何学来协调肿瘤发生。
Within the heterogeneous architecture of tumour tissue there exists an elusive population of stem-like cells that are implicated in both recurrence and metastasis(1,2). Here, by using engineered extracellular matrices, we show that geometric features at the perimeter of tumour tissue will prime a population of cells with a stem-cell-like phenotype. These cells show characteristics of cancer stem cells in vitro, as well as enhanced tumorigenicity in murine models of primary tumour growth and pulmonary metastases. We also show that interfacial geometry modulates cell shape, adhesion through integrin alpha(5)beta(1), MAPK and STAT activity, and initiation of pluripotency signalling. Our results for several human cancer cell lines suggest that interfacial geometry triggers a general mechanism for the regulation of cancer-cell state. Similar to how a growing tumour can co-opt normal soluble signalling pathways(3), our findings demonstrate how cancer can also exploit geometry to orchestrate oncogenesis.