Probing the response of lung tumor cells to inflammatory microvascular endothelial cells on fluidic microdevice.

Abstract

The development of cancer depends on a complex tissue microenvironment for sustained growth, invasion, and metastasis. The extravasation of tumor cells is a critical event in tumor metastasis. However, the process and mechanism that underlie tumor cell extravasation remain unclear, which restricts the examination of many tumor processes and presents a formidable hurdle to drug development. To explore the initial steps by which lung tumor cells interact with the brain microvascular wall in the course of extravasation, we present a simple, inexpensive, and time-saving microfluidic device to mimic the inflammatory brain microvascular microenvironment and to investigate both the biochemical and mechanical causes of lung tumor cell rolling and adhesion on inflammatory endothelium to analyze the synergistic effects on tumor extravasation under fluidic shear stress conditions. Under microvascular inflammation induced by tumor necrosis factor α, the lung tumor cells (A549 cells) displayed significant adhesion activity. In addition, we found that this situation could be reversed by administration of Rho/Rho-associated protein serine/threonine kinase (ROCK) inhibitor (Y27632). We believe that this promising microdevice-based tumor adhesion and extravasation research platform can be used to study tumor behavior in an inflammatory vascular system and will make a valuable contribution for the investigation of the mechanism of tumor cell extravasation.