Department of Biomedical Engineering, Boston University, Boston, MA, USA.
Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA.
Nat Biomed Eng. 2023 Nov;7(11):1473-1492. doi: 10.1038/s41551-023-01080-8. Epub 2023 Aug 28.
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.
在癌症中，固体压力会阻碍治疗药物输送到肿瘤中，以及免疫细胞的运输和肿瘤浸润。了解这些后果和固体压力的起源需要在细胞尺度上在体内进行探测。在这里，我们报告了一种在体内进行固体压力体积和纵向测量的方法，以及该方法在肿瘤中的应用结果。我们使用多模式活体显微镜对注射到小鼠乳腺癌中的荧光标记聚丙烯酰胺珠进行了研究，并通过数学建模来比较单细胞和组织尺度、原发和转移瘤、体外和体内、活体小鼠和死后组织中的固体压力。我们发现，固体压力的传递是依赖于尺度的，肿瘤细胞所经历的压力低于其嵌入的组织，而肺部转移瘤中的肿瘤细胞所经历的固体压力比原发肿瘤中的肿瘤细胞要高得多。固体压力对长度尺度和微环境的依赖性可能为开发使癌细胞对这些机械力敏感的治疗方法提供信息。
