Title:
Investigating differential electrotaxis of glioblastoma and medulloblastoma spheroidal aggregates
Investigating differential electrotaxis of glioblastoma and medulloblastoma spheroidal aggregates
Author(s)
Lyon, Johnathan G.
Advisor(s)
Bellamkonda, Ravi V.
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Abstract
Treatment of brain and nervous system cancers remains a daunting clinical challenge, with one of the most common brain malignancies, glioblastoma, incurring a mere 5% five-year survival rate. In the search for new therapeutic means—specifically, new ways to direct or curb the invasion of brain cancers—we investigate the directed invasion of brain cancer cellular aggregates by an electrical field. This property is known as electrotaxis (or galvanotaxis), and is known to be involved in a variety of endogenous phenomena including tissue development and wound healing, and is purported to be involved in cancer invasion and metastasis. In this study, we explore electrotaxis in the context of brain cancer, and provide new insights into the effect’s underlying mechanisms. Here, we have developed an electrotaxis assay that adapts existing cancer invasion assays and allows us to study electrotaxis on aggregated populations of cells. We characterize glioblastoma and medulloblastoma cell lines in these assays and report on their electrotactic properties. We then investigate the transcriptome for two cell lines that were found to have opposing electrotactic responses, followed by pharmacological inhibition studies to further validate some of our findings. Overall, the hypotheses explored in this work advance our understanding of the pathways that underlie electrotactic sensing and steering and may lead to new means for guiding or managing brain malignancies.
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Date Issued
2017-11-02
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Text
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Dissertation