Endothelium and Subendothelial Matrix Mechanics Modulate Cancer Cell Transendothelial Migration.
Endothelium and Subendothelial Matrix Mechanics Modulate Cancer Cell Transendothelial Migration.
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DOI：
10.1002/advs.202206554
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发表时间：
2023-06
期刊：
影响因子：
15.1
通讯作者：
Moeendarbary, Emad
中科院分区：
文献类型：
--
作者：
Javanmardi, Yousef;Agrawal, Ayushi;Malandrino, Andrea;Lasli, Soufian;Chen, Michelle;Shahreza, Somayeh;Serwinski, Bianca;Cammoun, Leila;Li, Ran;Jorfi, Mehdi;Djordjevic, Boris;Szita, Nicolas;Spill, Fabian;Bertazzo, Sergio;Sheridan, Graham K.;Shenoy, Vivek;Calvo, Fernando;Kamm, Roger;Moeendarbary, Emad
关键词：
癌细胞外渗是转移级联中的关键步骤，涉及癌细胞在内皮上停滞、跨内皮迁移（TEM），然后侵入远处组织的内皮下细胞外基质（ECM）。虽然癌症研究主要集中在肿瘤细胞 (TC) 和 ECM 之间的生物力学相互作用，特别是在原发肿瘤部位，但人们对内皮细胞和内皮下 ECM 的机械特性以及它们如何促进外渗过程知之甚少。在这里，开发了一个综合的实验和理论框架来研究体外癌细胞外渗过程中 TC、内皮和内皮下 ECM 之间的机械串扰。研究发现，癌细胞富含肌动蛋白的突起会产生复杂的推拉力来启动和驱动 TEM，而迁移的成功也依赖于内皮产生的力。因此，介导内皮力的内皮下 ECM 的机械特性和内皮肌动球蛋白收缩性也会影响内皮细胞对癌细胞迁移的抵抗力。这些结果表明，远处组织的机械特征，包括内皮和内皮下 ECM 之间的力相互作用，是转移性器官向性的关键决定因素。结合先进的工程/材料科学、生物工具和计算/数学模拟来研究次要器官部位的内皮细胞和内皮下基质的机械特征如何影响癌症转移，特别是癌细胞的跨内皮迁移，这是外渗过程中的一个重要步骤。
Cancer cell extravasation, a key step in the metastatic cascade, involves cancer cell arrest on the endothelium, transendothelial migration (TEM), followed by the invasion into the subendothelial extracellular matrix (ECM) of distant tissues. While cancer research has mostly focused on the biomechanical interactions between tumor cells (TCs) and ECM, particularly at the primary tumor site, very little is known about the mechanical properties of endothelial cells and the subendothelial ECM and how they contribute to the extravasation process. Here, an integrated experimental and theoretical framework is developed to investigate the mechanical crosstalk between TCs, endothelium and subendothelial ECM during in vitro cancer cell extravasation. It is found that cancer cell actin‐rich protrusions generate complex push–pull forces to initiate and drive TEM, while transmigration success also relies on the forces generated by the endothelium. Consequently, mechanical properties of the subendothelial ECM and endothelial actomyosin contractility that mediate the endothelial forces also impact the endothelium's resistance to cancer cell transmigration. These results indicate that mechanical features of distant tissues, including force interactions between the endothelium and the subendothelial ECM, are key determinants of metastatic organotropism. A combination of advanced engineering/material sciences, biological tools, and computational/ mathematical simulations are employed to study how the mechanical features of both endothelial cells and the subendothelial matrix at secondary organ sites may influence cancer metastasis and, in particular, the transendothelial migration of cancer cells, which is a major step during the extravasation process.
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影响因子：
7.8
作者：
Wang, Hui;Fu, Weili;Im, Jae Hong;Zhou, Zengyi;Santoro, Samuel A;Iyer, Vandana;DiPersio, C Mike;Yu, Qian-Chun;Quaranta, Vito;Al-Mehdi, Abu;Muschel, Ruth J
通讯作者：
Muschel, Ruth J
DOI：
10.1007/s10555-020-09942-2
发表时间：
2021-03
期刊：
Cancer metastasis reviews
影响因子：
--
作者：
Cheng X;Cheng K
通讯作者：
Cheng K
影响因子：
4.6
作者：
Ferruzzi, J.;Sun, M.;Zaman, M. H.
通讯作者：
Zaman, M. H.
DOI：
10.1002/hep.28450
发表时间：
2016-07
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Desai SS;Tung JC;Zhou VX;Grenert JP;Malato Y;Rezvani M;Español-Suñer R;Willenbring H;Weaver VM;Chang TT
通讯作者：
Chang TT
DOI：
10.1039/c3ib40149a
发表时间：
2013-10
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
--
作者：
Chen MB;Whisler JA;Jeon JS;Kamm RD
通讯作者：
Kamm RD