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 (\(< 10 \, \mu {\text{m}}\)). 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.

中文翻译：

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循环肿瘤细胞与微血管壁之间的滚动和牢固粘附相互作用的定位。

 介绍

肿瘤细胞与血管壁的粘附是癌症转移的关键阶段。癌细胞牢固粘附后通常会通过内皮外渗。尽管先前的研究确定了癌细胞与平面基底的粘附行为的影响参数，但对癌细胞与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知之甚少。我们研究的目的是表征可变形循环细胞（DCC）牢固粘附或在壁上滚动的微脉管系统的尺寸，并确定促进这种牢固粘附的参数和驱动粘附相互作用的潜在机制。

 方法

DCC 的三维模型用于模拟 DCC 与周围流体之间的流固相互作用。动态粘附模型，其中粘附分子被建模为弹簧，用于使用动力学速率表达式来表示随机受体-配体相互作用。

 结果

我们的结果表明，细胞变形性和低剪切流率都促进了 DCC 在小血管中的牢固粘附 ( \(< 10 \, \mu {\text{m}}\) )。我们的研究结果表明，PSGL-1-P-选择素的配体-受体键可能导致 DCC 在较小的血管中牢固粘附，并在较大的血管中导致 DCC 滚动粘附，其中细胞速度下降，以促进整合素-ICAM-1 键的激活。

 结论

我们的研究提供了一个框架，可以准确预测不同 DCC 类型可能在微血管系统中牢固粘附的位置，并建立使癌细胞易于粘附的标准。