Intravital measurements of solid stresses in tumours reveal length-scale and microenvironmentally dependent force transmission.
Intravital measurements of solid stresses in tumours reveal length-scale and microenvironmentally dependent force transmission.
复制标题
肿瘤中固体应力的活体测量揭示了长度尺度和微环境依赖性的力传递。
DOI：
10.1038/s41551-023-01080-8
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发表时间：
2023
影响因子：
28.1
通讯作者：
Nia,HadiT
中科院分区：
文献类型：
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作者：
Zhang,Sue;Grifno,Gabrielle;Passaro,Rachel;Regan,Kathryn;Zheng,Siyi;Hadzipasic,Muhamed;Banerji,Rohin;O'Connor,Logan;Chu,Vinson;Kim,SungYeon;Yang,Jiarui;Shi,Linzheng;Karrobi,Kavon;Roblyer,Darren;Grinstaff,MarkW;Nia,HadiT
在癌症中，固体应力阻碍了向肿瘤提供治疗药物以及免疫细胞的运输和肿瘤浸润。了解这种后果和固体应力的起源需要在细胞尺度上进行体内探测。在这里，我们报告了一种对体内固体应力进行体积和纵向测量的方法，及其对肿瘤的适用性的结果。我们使用多模态活体显微镜对注射到小鼠乳腺肿瘤中的荧光标记聚丙烯酰胺珠进行观察，并使用数学模型来比较单细胞和组织尺度、原发性和转移性肿瘤、体外和小鼠体内以及活体小鼠和死后组织中的固体应力。我们发现，固体应力传递具有尺度依赖性，肿瘤细胞所承受的应力低于其包埋组织，而肺转移瘤中的肿瘤细胞所承受的固体应力明显高于原发肿瘤中的固体应力。固体应力对长度尺度和微环境的依赖性可能有助于开发使癌细胞对这种机械力敏感的疗法。
In cancer, solid stresses impede the delivery of therapeutics to tumours and the trafficking and tumour infiltration of immune cells. Understanding such consequences and the origin of solid stresses requires their probing in vivo at the cellular scale. Here we report a method for performing volumetric and longitudinal measurements of solid stresses in vivo, and findings from its applicability to tumours. We used multimodal intravital microscopy of fluorescently labelled polyacrylamide beads injected in breast tumours in mice as well as mathematical modelling to compare solid stresses at the single-cell and tissue scales, in primary and metastatic tumours, in vitro and in mice, and in live mice and post-mortem tissue. We found that solid-stress transmission is scale dependent, with tumour cells experiencing lower stresses than their embedding tissue, and that tumour cells in lung metastases experience substantially higher solid stresses than those in the primary tumours. The dependence of solid stresses on length scale and the microenvironment may inform the development of therapeutics that sensitize cancer cells to such mechanical forces.