Date on Master's Thesis/Doctoral Dissertation

5-2024

Document Type

Master's Thesis

Degree Name

M.S.

Department

Bioengineering

Committee Chair

Chen, Joseph

Committee Member

Frieboes, Hermann

Committee Member

Hawkins, Nick

Author's Keywords

Glioblastoma; mechanobiological; intratumoral

Abstract

Glioblastoma diagnosis has one of the lowest average life expectancies at only 14 months. Recurrent tumor formation and progression despite aggressive chemotherapy and radiation significantly contributes to the poor prognosis. Recurrence is likely due to mesenchymal cells breaking off from the primary tumor, infiltrating the parenchyma to establish secondary tumors. Mesenchymal cells initially undergo an epithelial to mesenchymal transition, characterized by a loss of cell-cell adhesion, increased migration and increased proliferation. While this transition can be chemically induced, there is a gap of understanding surrounding physical activation of this pathway. The tumor microenvironment is mechanically active with the cells responding to shear stress, tensile stress, and even compressive stress. Compression largely happens when the tumor sphere expands into the surrounding tissue, experiencing normal force pushing back from all directions. This force is expectantly high in the brain as the surrounding tissue is dense, increasing the normal force against the surrounding tissue. This phenomena is largely understudied due to the lack of appropriate in-vitro testing mechanisms, but could be a predominant driver in the mesenchymal behavior responsible for secondary tumor formation. Development of a 3D system will allow investigation into forces experienced during expansion, invasion, and secondary tumor establishment. The mechanisms behind these changes in force can be studied at a biomolecular level with the development of a 2D compression system. This thesis aims to show development of these two systems, the confirmation of viability, and initial results.

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