Cancer Biophysics Laboratory, Department of Mechanical and Manufacturing Engineering, University of Cyprus, Nicosia, Cyprus.
Biomech Model Mechanobiol. 2023 Oct;22(5):1625-1643. doi: 10.1007/s10237-023-01716-3. Epub 2023 May 2.
Mechanical stresses in solid tumors play an important role in tumor progression and treatment efficacy but their quantification is under-investigated. Here, we developed an experimental and computational approach to calculate growth-induced, residual stresses and applied it to the breast (4T1), pancreatic (PAN02), and fibrosarcoma (MCA205) tumor models. Following resection, tumors are embedded in agarose gels and cuts are made in two perpendicular directions to release residual stress. With the use of image processing, the detailed bulging displacement profile is measured and finite elements models of the bulging geometry are developed for the quantification of the stress levels. The mechanical properties of the tumors are measured in vivo prior to resection with shear wave elastography. We find that the average magnitude of residual stresses ranges from 3.31 to 10.88 kPa, and they are non-uniformly distributed within the tissue due to the heterogeneity of the tumor microenvironment. Interestingly, we demonstrate that a second cut can still release a significant amount of stresses. We further find a strong association of spatial hyaluronan and collagen content with the spatial profile of stress for the MCA205 and PAN02 tumors and a partial association for the 4T1. Interestingly the colocalization of hyaluronan and collagen content had a stronger association with the spatial profile of stress for MCA205, PAN02, and 4T1. Finally, measurements of the elastic modulus with shear wave elastography show a nonlinear correlation with tumor volume for the more fibrotic MCA205 and 4T1 tumors. Overall, our results provide insights for a better understanding of the mechanical behavior of tumors.
实体瘤中的机械应力在肿瘤进展和治疗效果中起着重要作用，但对其量化的研究还不够充分。在这里，我们开发了一种实验和计算方法来计算生长诱导的残余应力，并将其应用于乳腺（4T1）、胰腺（PAN02）和纤维肉瘤（MCA205）肿瘤模型。切除后，将肿瘤嵌入琼脂糖凝胶中，并在两个垂直方向上进行切割以释放残余应力。通过图像处理，测量详细的凸起位移轮廓，并为凸起几何形状开发有限元模型，以量化应力水平。在切除前，使用剪切波弹性成像术在体内测量肿瘤的力学性能。我们发现残余应力的平均幅度范围为 3.31 至 10.88 kPa，由于肿瘤微环境的异质性，它们在组织内不均匀分布。有趣的是，我们证明第二次切割仍然可以释放大量的应力。我们进一步发现，空间透明质酸和胶原蛋白含量与 MCA205 和 PAN02 肿瘤的应力空间分布具有很强的相关性，而与 4T1 肿瘤的相关性则部分相关。有趣的是，透明质酸和胶原蛋白含量的共定位与 MCA205、PAN02 和 4T1 的应力空间分布具有更强的相关性。最后，用剪切波弹性成像术测量弹性模量与更纤维化的 MCA205 和 4T1 肿瘤的肿瘤体积呈非线性相关。总的来说，我们的结果为更好地理解肿瘤的力学行为提供了一些见解。
