A microfluidic device for isolation and characterization of transendothelial migrating cancer cells.

Raymond H W Lam,Xin Cui,Weijin Guo,Dong Sun,Yubing Sun,Shuhuan Hu,Baoce Sun

doi:10.1063/1.4974012

Abstract

Transendothelial migration of cancer cells is a critical stage in cancer, including breast cancer, as the migrating cells are generally believed to be highly metastatic. However, it is still challenging for many existing platforms to achieve a fully covering endothelium and to ensure transendothelial migration capability of the extracted cancer cells for analyses with high specificity. Here, we report a microfluidic device containing multiple independent cell collection microchambers underneath an embedded endothelium such that the transendothelial-migrated cells can be selectively collected from only the microchambers with full coverage of an endothelial layer. In this work, we first optimize the pore size of a microfabricated supporting membrane for the endothelium formation. We quantify transendothelial migration rates of a malignant human breast cell type (MDA-MB-231) under different shear stress levels. We investigate characteristics of the migrating cells including morphology, cytoskeletal structures, and migration (speed and persistence). Further implementation of this endothelium-embedded microfluidic device can provide important insights into migration and intracellular characteristics related to cancer metastasis and strategies for effective cancer therapy.

Highlights

Breast cancer is well known as the second leading cause of cancer-related deaths among women.[1]
Transendothelial migration of cancer cells is a critical stage in cancer, including breast cancer, as the migrating cells are generally believed to be highly metastatic
We report a microfluidic device containing multiple independent cell collection microchambers underneath an embedded endothelium such that the transendothelial-migrated cells can be selectively collected from only the microchambers with full coverage of an endothelial layer

Summary

Introduction

Breast cancer is well known as the second leading cause of cancer-related deaths among women.[1] Remarkably, its metastasis, rather than the primary tumors, causes most of the deaths.[2] In the metastasis, tumor cells escaped to the bloodstream can further extravasate to distant tissues or organs through membranes of the lymphatic and hematogenous systems.[3] Understanding behaviors of the cancer cells migrated through vascular endothelial layers is essential to reveal fundamental mechanisms of metastasis as well as the related cancer therapeutics. Grow as an endothelium before seeding cancer cells.[6]. This approach allows researchers to monitor migration of cancer cells across the endothelium under a chemotactic gradient. It is still challenging to control fluidic conditions to mimic the bloodstream together with specific biochemical conditions such as a defined chemotactic gradient over time

Methods

Results

Conclusion