Liang Shile, Hoskins Meghan, Khanna Payal, Kunz Robert F, Dong Cheng
Department of Bioengineering, The Pennsylvania State University, 233 Hallowell Building, University Park, PA 16802, USA.
Cell Mol Bioeng. 2008 Sep 1;1(2-3):189-200. doi: 10.1007/s12195-008-0016-8.
The primary cause of cancer mortality is not attributed to primary tumor formation, but rather to the growth of metastases at distant organ sites. Tumor cell adhesion to blood vessel endothelium (EC) and subsequent transendothelial migration within the circulation are critical components of the metastasis cascade. Previous studies have shown polymorphonuclear neutrophils (PMNs) may facilitate melanoma cell adhesion to the EC and subsequent extravasation under flow conditions. The melanoma cell-PMN interactions are found to be mediated by the binding between intercellular adhesion molecule-1 (ICAM-1) on melanoma cells and β(2) integrin on PMNs and by endogenously secreted interleukin 8 (IL-8) within the tumor-leukocyte microenvironment. In this study, the effects of fluid convection on the IL-8-mediated activation of PMNs and the binding kinetics between PMNs and melanoma cells were investigated. Results indicate that the shear rate dependence of PMN-melanoma cell adhesion and melanoma cell extravasation is due, at least partly, to the convection of tumor-secreted proinflammatory cytokine IL-8.
癌症死亡的主要原因并非原发性肿瘤的形成，而是远处器官部位转移灶的生长。肿瘤细胞与血管内皮（EC）的黏附以及随后在循环系统中的跨内皮迁移是转移级联反应的关键组成部分。先前的研究表明，多形核中性粒细胞（PMN）可能会促进黑色素瘤细胞在流动条件下与EC的黏附以及随后的外渗。发现黑色素瘤细胞与PMN的相互作用是由黑色素瘤细胞上的细胞间黏附分子-1（ICAM-1）与PMN上的β(2)整合素之间的结合以及肿瘤-白细胞微环境中内源性分泌的白细胞介素8（IL-8）介导的。在本研究中，研究了流体对流对IL-8介导的PMN激活以及PMN与黑色素瘤细胞之间结合动力学的影响。结果表明，PMN-黑色素瘤细胞黏附以及黑色素瘤细胞外渗对剪切速率的依赖性至少部分归因于肿瘤分泌的促炎细胞因子IL-8的对流。
