Nia Hadi T, Liu Hao, Seano Giorgio, Datta Meenal, Jones Dennis, Rahbari Nuh, Incio Joao, Chauhan Vikash P, Jung Keehoon, Martin John D, Askoxylakis Vasileios, Padera Timothy P, Fukumura Dai, Boucher Yves, Hornicek Francis J, Grodzinsky Alan J, Baish James W, Munn Lance L, Jain Rakesh K
Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Leder Human Biology and Translational Medicine, Biology and Biomedical Sciences, Harvard Medical School, Boston MA 02115, USA.
Nat Biomed Eng. 2016;1. doi: 10.1038/s41551-016-0004. Epub 2016 Nov 28.
Solid stress and tissue stiffness affect tumour growth, invasion, metastasis and treatment. Unlike stiffness, which can be precisely mapped in tumours, the measurement of solid stresses is challenging. Here, we show that two-dimensional spatial mappings of solid stress and the resulting elastic energy in excised or tumours with arbitrary shapes and wide size ranges can be obtained via three distinct and quantitative techniques that rely on the measurement of tissue displacement after disruption of the confining structures. Application of these methods in models of primary tumours and metastasis revealed that: (i) solid stress depends on both cancer cells and their microenvironment; (ii) solid stress increases with tumour size; and (iii) mechanical confinement by the surrounding tissue significantly contributes to intratumoural solid stress. Further study of the genesis and consequences of solid stress, facilitated by the engineering principles presented here, may lead to significant discoveries and new therapies.
固体应力和组织硬度会影响肿瘤的生长、侵袭、转移及治疗。与可以在肿瘤中精确绘制的硬度不同,固体应力的测量具有挑战性。在此,我们表明,通过三种不同的定量技术,可以获得切除的或具有任意形状和广泛尺寸范围的肿瘤中固体应力和由此产生的弹性能的二维空间映射,这些技术依赖于在限制结构破坏后对组织位移的测量。将这些方法应用于原发性肿瘤和转移模型表明:(i)固体应力取决于癌细胞及其微环境;(ii)固体应力随肿瘤大小增加;(iii)周围组织的机械限制对肿瘤内固体应力有显著贡献。借助本文提出的工程原理对固体应力的起源和后果进行进一步研究,可能会带来重大发现和新疗法。