Honors Theses

Understanding Calcium Signaling Pathways in 3D Microfluidic Models of Glioblastoma Multiforme

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 malignant types of brain cancer and, therefore, highly fatal. Current lines of treatment include surgical resection, radiation, and chemotherapy, all of which GBM resists due to the complexity of GBM tumors, cells, and their microenvironment. Numerous research studies have been conducted to understand the oncogenesis, invasion mechanisms, and cellular characteristics of GBM. One specific mechanism that has caught the attention of researchers is calcium signaling, which plays a significant role in cell proliferation, resistance to treatment, and metastatic-related processes. Emerging targets for calcium signaling include transient receptor potential channels (TRP), a family of channels that mediate Ca2+ signaling and play a role in GBM development and invasion. This study examines and compares calcium signaling in non-invasive and invasive phenotypes of GBM. This has been done by generating a migrating cell model consisting of GBM spheroids placed into a Polydimethylsiloxane (PDMS) microfluidic device. I observed the cells sprouting from the spheroid and measured cytosolic calcium levels using dye for both the non-invasive and invasive phenotypes. It was hypothesized that more calcium would be associated with the invasive GBM model than the non-invasive one. This hypothesis was tested using spheroids from three GBM cell lines: A-172, U118MG, and U87MG. This enabled us to examine common invasion responses and characteristics across GBM cell lines. Here, we found that calcium fluorescence signals are significantly higher for spheroids in contact with the channels than for those not in contact with the channels for U118MG and U87MG. These two cell lines also have induced sprouting effects due to the physical confinements of the device. This project presents a relationship between increased sprouting and activated calcium signaling, laying the groundwork for new therapies to limit GBM migration and prevent further metastasis of this cancer by targeting the calcium signaling pathways.

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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