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首页> 外文期刊>Cellular and Molecular Bioengineering >Localization of Rolling and Firm-Adhesive Interactions Between Circulating Tumor Cells and the Microvasculature Wall
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Localization of Rolling and Firm-Adhesive Interactions Between Circulating Tumor Cells and the Microvasculature Wall

机译：循环肿瘤细胞和微血管壁之间的轧制和牢固相互作用的定位

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Introduction The adhesion of tumor cells to vessel wall is a critical stage in cancer metastasis. Firm adhesion of cancer cells is usually followed by their extravasation through the endothelium. Despite previous studies identifying the influential parameters in the adhesive behavior of the cancer cell to a planer substrate, less is known about the interactions between the cancer cell and microvasculature wall and whether these interactions exhibit organ specificity. The objective of our study is to characterize sizes of microvasculature where a deformable circulating cell (DCC) would firmly adhere or roll over the wall, as well as to identify parameters that facilitate such firm adherence and underlying mechanisms driving adhesive interactions. Methods A three-dimensional model of DCCs is applied to simulate the fluid-structure interaction between the DCC and surrounding fluid. A dynamic adhesion model, where an adhesion molecule is modeled as a spring, is employed to represent the stochastic receptor-ligand interactions using kinetic rate expressions. Results Our results reveal that both the cell deformability and low shear rate of flow promote the firm adhesion of DCC in small vessels (<10 mu m). Our findings suggest that ligand-receptor bonds of PSGL-1-P-selectin may lead to firm adherence of DCC in smaller vessels and rolling-adhesion of DCC in larger ones where cell velocity drops to facilitate the activation of integrin-ICAM-1 bonds. Conclusions Our study provides a framework to predict accurately where different DCC-types are likely to adhere firmly in microvasculature and to establish the criteria predisposing cancer cells to such firm adhesion.
机译：简介肿瘤细胞对血管壁的粘附是癌症转移的关键阶段。癌细胞的坚固粘附通常通过内皮的外渗。尽管先前的研究鉴定了癌细胞的粘合剂行为中的影响参数，但较少关于癌细胞和微血管壁之间的相互作用，以及这些相互作用是否表现出器官特异性。我们的研究目的是表征微孔血管系的尺寸，其中可变形循环电池（DCC）牢固地粘附或滚过壁，以及识别促进这种坚固粘附和驱动粘合剂相互作用的底层机制的参数。方法应用DCC的三维模型来模拟DCC和周围流体之间的流体结构相互作用。使用粘合分子作为弹簧建模的动态粘合模型用于表示使用动力学率表达的随机受体 - 配体相互作用。结果我们的研究结果表明，电池可变形性和低剪切速率均促进DCC在小容器中的粘附（<10μm）。我们的研究结果表明，PSGL-1-P-SELETIN的配体接受键可能导致DCC在较小的血管中坚固的DCC粘附，DCC在较大的血管中的滚动 - 粘附，其中细胞速度下降以促进整联ICAM-1键的活化。结论我们的研究提供了一种框架，可以准确地预测，其中不同的DCC型可能牢固地粘附在微血管系统中，并将预测癌细胞的标准粘附到这种牢固的附着力。

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