The effects of luminal and trans-endothelial fluid flows on the extravasation and tissue invasion of tumor cells in a 3D in vitro microvascular platform.

The effects of luminal and trans-endothelial fluid flows on the extravasation and tissue invasion of tumor cells in a 3D in vitro microvascular platform.
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DOI:
10.1016/j.biomaterials.2020.120470
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发表时间:
2021-01
期刊:
影响因子:
14
通讯作者:
Kamm RD
Kamm RD
中科院分区:
工程技术1区
文献类型:
--
作者:
Hajal C;Ibrahim L;Serrano JC;Offeddu GS;Kamm RD

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在转移性播散的整个过程中,肿瘤细胞持续地受到由于其局部微环境中的压力变化而引起的复杂流体流动所产生的机械力。虽然这些力量与3D基质中的侵袭性表型相关,但它们在转移级联的关键步骤中的作用,即外渗和随后的间质迁移,仍然知之甚少。在这项研究中,在人体微血管系统的体外模型进行肿瘤细胞的生理管腔,跨内皮,和间质流,以评估其对这些转移的关键步骤的影响。管腔血流促进了肿瘤细胞的外渗潜力,这可能是由于它们增加了血管内迁移速度。跨内皮流动增加了肿瘤细胞穿过内皮的速度以及它们在外渗后在基质中的迁移速度。此外,肿瘤细胞具有更大的倾向,迁移在靠近内皮细胞时,受到生理流动,这可能会促进转移灶的成功形成。这些结果表明,在外渗和侵袭过程中,流体流动的重要作用,它可以决定肿瘤细胞的局部转移潜力。
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.
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