Activation of cell migration via morphological changes in focal adhesions depends on shear stress in MYCN-amplified neuroblastoma cells

Takumi Hiraiwa,Norihisa Miki,Takahiro G Yamada,Noriko Hiroi,Akira Funahashi

doi:10.1098/rsif.2018.0934

Abstract

Neuroblastoma is the most common solid tumour of childhood, and it metastasizes to distant organs. However, the mechanism of metastasis, which generally depends on the cell motility of the neuroblastoma, remains unclear. In many solid tumours, it has been reported that shear stress promotes metastasis. Here, we investigated the relationship between shear stress and cell motility in the MYCN-amplified human neuroblastoma cell line IMR32, using a microfluidic device. We confirmed that most of the cells migrated downstream, and cell motility increased dramatically when the cells were exposed to a shear stress of 0.4 Pa, equivalent to that expected in vivo. We observed that the morphological features of focal adhesion were changed under a shear stress of 0.4 Pa. We also investigated the relationship between malignancy and the motility of IMR32 cells under shear stress. Decreasing the expression of MYCN in IMR32 cells via siRNA transfection inhibited cell motility by a shear stress of 0.4 Pa. These results suggest that MYCN-amplified neuroblastoma cells under high shear stress migrate to distant organs due to high cell motility, allowing cell migration to lymphatic vessels and venules.

Highlights

Migration of cancer cells towards lymphatic vessels and blood vessels is thought to be a critical step for distant metastasis [1,2]
We found that the motility of IMR32 cells is affected by shear stress
These findings suggest that shear stress increases the motility of MYCN-amplified neuroblastoma cells in vivo without including cell death

Summary

Introduction

Migration of cancer cells towards lymphatic vessels and blood vessels is thought to be a critical step for distant metastasis [1,2]. Researchers have proposed that in vivo shear stress promotes the access of cancer cells to lymphatic vessels and blood vessels [3,4,5,6,7]. Cancer cells in the stromal space are exposed to shear stress caused by the interstitial flow [5]. Many types of cancer cell have the ability to respond to various scales of shear stress (table 1). Neuroblastoma cells metastasize to distant organs [13], but the mechanism of this metastasis remains unclear. We hypothesized that the migration of malignant neuroblastoma cells is affected by shear stress

Methods

Results

Conclusion