Honors Theses

Understanding the Epithelial to Mesenchymal Transition of Glioblastoma Multiforme on a Microfluidic Model

Advisor

Loan Bui, Ph.D.

Department

Biology

Publication Date

4-23-2025

Document Type

Honors Thesis

Abstract

Glioblastoma Multiforme (GBM) is one of the most aggressive and fatal forms of brain cancer. Despite the multiple advances in treatment, median survival is only about 15 months upon diagnosis. Hence, multiple studies have been conducted to enhance understanding of GBM tumor biology and the mechanisms underlying its malignancy. This invasive behavior is strongly influenced by Epithelial to Mesenchymal Transition (EMT), a phenotypic shift that enhances motility and therapeutic resistance. Transforming Growth Factor-β (TGF-β) is a key regulator of EMT. In this study, we investigated the effect of TGF-β inhibition on GBM invasion using a microfluidic platform that mimics the confined geometry of the brain tumor microenvironment. GBM spheroids (U-87 MG, LN-229, U-118 MG) were embedded in Matrigel and exposed to SB-431542, a selective inhibitor of the TGF-β type I receptor. Invasion was assessed by tracking spheroid sprouting under treated and untreated conditions. The results indicate that TGF-β inhibition significantly reduces spheroid invasion across all three GBM cell lines when placed against the channels. These findings support the hypothesis that EMT contributes to the invasive phenotype of GBM under conditions of physical confinement. The findings of this study broadened our understanding of the complexity of EMT and its role in GBM cancer development and metastasis. Moreover, this work highlights the potential of combining microfluidic modeling with molecular intervention to dissect invasion mechanisms and evaluate candidate therapeutics.

Permission Statement

This item is protected by copyright law (Title 17, U.S. Code) and may only be used for noncommercial, educational, and scholarly purposes.

Keywords

Undergraduate research

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