Effects of Compressive Stress on Glioblastoma Cells

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Date

2017-05

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The Ohio State University

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Abstract

The application of engineering principles and technologies to biological systems has enabled the advent of new healthcare strategies. This research is focused on understanding the effects of compression on the migration of brain tumor cells in vitro and to understand the molecular underpinnings regarding this change. Compression in the brain arises as a result of the barrier formed by the cranium. As intracranial pressure increases, because of head injury or tumor growth, compression will increase. Untreated compression in the brain can lead to the destruction of brain tissue and even death. Previous studies have shown that increasing compression on breast cancer cells leads to an increase in migration. The increase in migration of cancer cells in comparison to somatic cells may explain a portion of the invasive nature of cancer cells. We examined the effects of different compressive forces applied to cells and how force affects migration using three types of glioblastoma brain cancer cells. To assess cell migration and proliferation, a traditional wound healing assay was employed, as well as a 3D single cell migration assay that evaluates the multi-directionality of cell migration. To complete the 3D migration assay, a hydrogel was engineered to have the specific viscosity and elasticity that mimics the environment of the brain. We found that increasing the pressure (compression) above 23 Pa causes a decrease in the migration of the glioblastoma cells. Additionally, to determine how the compressive stress affects the cells, a single cell morphology experiment was completed, which indicated that compressive stress decreases cell area and ferret length. This conclusion contrasts with the previous research model that described the link between compressive stress and migration for breast cancer cells. Our long-term objective from this research is to elucidate the effect of compressive solid stress on glioblastoma cell migration to identify possible drug interventions and to translate this finding to the clinical treatment.

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Keywords

Glioblastoma, Compressive Stress, Mechanical Stress, invasive phenotype

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