Hajal Cynthia, Ibrahim Lina, Serrano Jean Carlos, Offeddu Giovanni S, Kamm Roger D
Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Biomaterials. 2021 Jan;265:120470. doi: 10.1016/j.biomaterials.2020.120470. Epub 2020 Oct 19.
Throughout the process of metastatic dissemination, tumor cells are continuously subjected to mechanical forces resulting from complex fluid flows due to changes in pressures in their local microenvironments. While these forces have been associated with invasive phenotypes in 3D matrices, their role in key steps of the metastatic cascade, namely extravasation and subsequent interstitial migration, remains poorly understood. In this study, an in vitro model of the human microvasculature was employed to subject tumor cells to physiological luminal, trans-endothelial, and interstitial flows to evaluate their effects on those key steps of metastasis. Luminal flow promoted the extravasation potential of tumor cells, possibly as a result of their increased intravascular migration speed. Trans-endothelial flow increased the speed with which tumor cells transmigrated across the endothelium as well as their migration speed in the matrix following extravasation. In addition, tumor cells possessed a greater propensity to migrate in close proximity to the endothelium when subjected to physiological flows, which may promote the successful formation of metastatic foci. These results show important roles of fluid flow during extravasation and invasion, which could determine the local metastatic potential of tumor cells.
在转移扩散过程中，肿瘤细胞不断受到局部微环境压力变化所导致的复杂流体流动产生的机械力作用。虽然这些力已被证明与肿瘤细胞在三维基质中的侵袭表型有关，但其在转移级联反应的关键步骤，即渗出和随后的间质迁移中所起的作用，仍知之甚少。在本研究中，采用了一种人体微血管的体外模型，使肿瘤细胞受到生理性的管腔、跨内皮和间质流动，以评估其对转移关键步骤的影响。管腔流动促进了肿瘤细胞的渗出潜能，这可能是由于其血管内迁移速度增加所致。跨内皮流动增加了肿瘤细胞穿过内皮的迁移速度以及渗出后在基质中的迁移速度。此外，当受到生理性流动作用时，肿瘤细胞更倾向于在内皮附近迁移，这可能促进转移灶的成功形成。这些结果表明流体流动在渗出和侵袭过程中起着重要作用，这可能决定肿瘤细胞的局部转移潜能。
