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.

Chemoresistance in mesenchymal lung cancer cells is correlated to high regulatory T cell presence in the tumor microenvironment

“…Microfluidic devices are finding increasing and innovative use both in defining the role of immune microenvironment in lung tumorigenesis as well as potentially a prognostic indicator when targeted immunotherapy is used . Both gain of CD25 and fibronectin expression can potentially be used in designing microfluidic sensor devices for detecting the lung tumor microenvironment and response to chemotherapy.…”

Microfluidic applications on circulating tumor cell isolation and biomimicking of cancer metastasis

“…5A, Xu et al. introduced a microfluidic device to mimic inflammatory brain microvascular microenvironment and to investigate rolling and adhesion of tumor cells under fluidic shear stress [103]. Bai et al.…”

“…(A) The microfluidic device for studying tumor cells rolling and adhesion using lung cancer cells [103]; reproduced by permission of John Wiley and Sons. (B) The microfluidic device for modelling EMT process using A549 human lung cancer cells [110]; reproduced by permission of John Wiley and Sons.…”

Microfluidics for studying metastatic patterns of lung cancer

“…Presented microfluidic systems were applied to study the different stages of lung cancers metastasis. The figures are reproduced from Li et al [8] with permission of Applied Biochemistry and Biotechnology, Kim et al [13] and Xu et al [72] with permission of Electrophoresis, Benoit et al [73] with permission of Applied and Environmental Microbiology, Guo et al [74] with permission of Biochemical and Biophysical Research Communications, Yu et al [75] and Bai et al [14] with permission of Oncotarget, Zhao et al [47] with permission of Scientific Reports, Wang et al [9] and Anguiano et al [5] with permission of Plos One, Cui et al [76] and Kao et al [77] with permission of Biomicrofluidics, Zou et al [78] with the permission of Analytical Chemistry, Tata et al [38] with permission of Advances in Natural Sciences: Nanoscience and Nanotechnology, Huang et al [39] and Li et al [79] with permission of Biosensors and Bioelectronics, Li et al [80] with the permission of Analytical and Bioanalytical Chemistry…”