Shear stress and shear rate differentially affect the multi-step process of leukocyte-facilitated melanoma adhesion
Shear stress and shear rate differentially affect the multi-step process of leukocyte-facilitated melanoma adhesion
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DOI：
10.1016/j.yexcr.2005.07.028
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发表时间：
2005-11-01
影响因子：
3.7
通讯作者：
Dong, C
中科院分区：
文献类型：
--
作者：
Liang, S;Slattery, MJ;Dong, C
先前的研究已经表明中性粒细胞（PMN）促进黑素瘤细胞外渗[M. J. Slattery，C. Dong，中性粒细胞在流动条件下影响黑色素瘤粘附和迁移，Intl. J. Cancer 106（2003）713-722]然而，关于PMN、黑素瘤和内皮（EC）之间的特异性相互作用或在流动条件下涉及的分子机制知之甚少。本研究的目的是调查一个“两步粘附”的假设，涉及初始中性粒细胞拴系的EC和随后的黑色素瘤细胞被捕获拴系的中性粒细胞。利用平行板流动室分析了流体动力学剪切应力和剪切速率的不同影响。结果表明，一个新的发现，PNIN促进黑色素瘤细胞阻滞EC调制的剪切速率，这是成反比的细胞-细胞接触时间，而不是由剪切应力，这是成比例的力施加在形成的债券。β（2）整合素/ICAM-1粘附机制，结果表明LFA-1和Mac-1在剪切条件下协同介导PMN-EC-黑色素瘤相互作用。此外，内源性产生的IL-8有助于通过PMN上的CXC趋化因子受体1和2（CXCR 1和CXCR 2）在EC上阻止PMN促进的黑色素瘤。这些结果提供了新的证据的复杂作用的血流动力学的力量，分泌的趋化因子和PMN-黑色素瘤粘附在招聘转移性癌细胞的EC。(c)2005年爱思唯尔公司All rights reserved.
Previous studies have shown that neutropbils (PMNs) facilitate melanoma cell extravasation [M.J. Slattery, C. Dong, Neutrophils influence melanoma adhesion and migration under flow conditions, Intl. J. Cancer 106 (2003) 713-722] Little is known, however, about the specific interactions between PMNs, melanoma and the endothelium (EC) or the molecular mechanism involved under flow conditions. The aim of this study is to investigate a "two-step adhesion" hypothesis that involves initial PMN tethering on the EC and subsequent melanoma cells being captured by tethered PMNs. Different effects of hydrodynamic shear stress and shear rate were analyzed using a parallel-plate flow chamber. Results indicate a novel finding that PNIN-facilitated melanoma cell arrest on the EC is modulated by shear rate, which is inversely-proportional to cell-cell contact time, rather than by the shear stress, which is proportional to the force exerted on formed bonds. beta(2) integrins/ICAM-1 adhesion mechanisms were examined and the results indicate LFA-1 and Mac-1 cooperate to mediate the PMN-EC-melanoma interactions under shear conditions. In addition, endogenously produced IL-8 contributes to PMN-facilitated melanoma arrest on the EC through the CXC chemokine receptors 1 and 2 (CXCR1 and CXCR2) on PMN. These results provide new evidence for the complex role of hemodynamic forces, secreted chemokines and PMN-melanoma adhesion in the recruitment of metastatic cancer cells to the EC. (c) 2005 Elsevier Inc. All rights reserved.