Tapered Microtract Array Platform for Antimigratory Drug Screening of Human Glioblastoma Multiforme

Abstract

Understanding the effects of topographic characteristics on tumor cell migration is important for the development of new anti-migratory therapies. However, simplified in vitro culture systems often lead to inaccurate results regarding the efficacy of drugs. Histopathologically, glioblastoma multiform (GBM) cells migrate along the orientation of thin, elongated anatomical structures, such as white-matter tracts. Here, a tapered microtract array platform which mimics the anatomical features of brain tissue is introduced. This platform enables optimization of design for platform fabrication depending on topographic effects. By monitoring the migration of GBM cells on a simple tapered microtract, a saltatory migration resembling the migratory phenotype of human GBM cells in vivo is observed. The platform effectively induces the native characteristics and behavior of cells by topographic cues, allowing to observe the critical point for crawling to saltatory transition. Furthermore, this platform can be applied to efficiently screen anti-cancer drug by inhibiting associated signaling pathways on GBM cells. In conclusion, the microtract array platform reported here may provide a better understanding of the effects of topographic characteristics on cell migration, and may also be useful to determine the efficacy of antimigratory drugs for glioblastoma cells with cellular and molecular research and high-throughput screening.

Mechanical confinement triggers glioma linear migration dependent on formin FHOD3

“…In that configuration, hyaluronic acid inhibits glioma motility ( Rape and Kumar, 2014 ). Cha et al. (2014 ) found that thin, tapered microtracks coated with laminin allow glioma cells to move in a saltatory motion, similar to our observations.…”

“…, 2011 ; Rao et al. , 2013 ) and a saltatory mode of motility ( Cha et al. , 2014 ), with actin bundles parallel to the axis of the lines ( Pathak and Kumar, 2012 ).…”

Strategies of Mesenchymal Invasion of Patient-derived Brain Tumors: Microenvironmental Adaptation

“…Numerous culture models, such as in vitro three-dimensional (3D) hydrogels, ex vivo organotypic brain slice cultures, and in vivo mouse models, have been used to study the cellular effects on microenvironment 11 16 17 18 19 20 21 22 23 24 . These research have indicated that the glioblastoma cells migrate individually with the mesenchymal mode of motility in a traction-dependent manner, so called saltatory migration 25 26 27 . In this process, the GBM cells generate a strong adhesion force at the focal contacts on ECM by intensively concentrating the integrins 25 .…”

Biomimetic Strategies for the Glioblastoma Microenvironment

“…Recently, there have been reports on the effect of 2D topography on GBM invasion, replicating the in vivo behavior of GBM cells (Cha et al, 2015;Smith et al, 2016;Sim et al, 2017). For instance, using 2D polydimethylsiloxane (PDMS) substrates, the tapered microtract of the gradient width ranging from 3 to 100 µm was fabricated to identify the effect of topography on GBM motility (Cha et al, 2015).…”