Investigation of Tumor Cell Behaviors on a Vascular Microenvironment-Mimicking Microfluidic Chip.

Rong Huang,Yunze Long,Xingyu Jiang,Wenwen Liu,Wenfu Zheng,Wei Zhang

doi:10.1038/srep17768

Abstract

The extravasation of tumor cells is a key event in tumor metastasis. However, the mechanism underlying tumor cell extravasation remains unknown, mainly hindered by obstacles from the lack of complexity of biological tissues in conventional cell culture, and the costliness and ethical issues of in vivo experiments. Thus, a cheap, time and labor saving, and most of all, vascular microenvironment-mimicking research model is desirable. Herein, we report a microfluidic chip-based tumor extravasation research model which is capable of simultaneously simulating both mechanical and biochemical microenvironments of human vascular systems and analyzing their synergistic effects on the tumor extravasation. Under different mechanical conditions of the vascular system, the tumor cells (HeLa cells) had the highest viability and adhesion activity in the microenvironment of the capillary. The integrity of endothelial cells (ECs) monolayer was destroyed by tumor necrosis factor-α (TNF-α) in a hemodynamic background, which facilitated the tumor cell adhesion, this situation was recovered by the administration of platinum nanoparticles (Pt-NPs). This model bridges the gap between cell culture and animal experiments and is a promising platform for studying tumor behaviors in the vascular system.

Highlights

Tumor metastasis, leading to over 90% of all tumor-related deaths, is a complex, multistep process including growth, local invasion, intravasation, circulation in blood/lymphatic system, extravasation, and eventually form metastases in remote organs/tissues[1]
We studied individual or synergistic effects of mechanical and biochemical factors on the behavior of tumor cells, especially their adhesion, on the model
Accumulating evidence indicated that hypertension induced by vascular endothelial growth factor (VEGF) inhibitor is closely related to survival ratio of the cancer patients[26,27]

Summary

Introduction

Tumor metastasis, leading to over 90% of all tumor-related deaths, is a complex, multistep process including growth, local invasion, intravasation, circulation in blood/lymphatic system, extravasation, and eventually form metastases in remote organs/tissues[1]. During the intravasation, circulation in vascular system, and extravasation, tumor cells must undergo considerable mechanical stimulations including deformations of tumor cells[14] and hemodynamic forces including fluid shear stress (FSS) and cyclic stretch (CS)[15]. All of these mechanical stimulations could affect survival of the tumor cells and their ability to establish metastatic foci[16]. In a physiological mechanical background, as a typical biomechanical factor, TNF-α destroyed the integrity of the ECs monolayer and facilitated the HeLa cell adhesion This model would be an ideal platform for investigation of tumor cell behaviors in the vascular system

Methods

Results

Conclusion