Degree

Doctor of Philosophy (PhD)

Department

Chemistry

Document Type

Dissertation

Abstract

In vitro multicellular spheroids are attractive model systems for assessing genetic and epigenetic changes that occur in diseased tissues. Understanding how such alterations in gene and subsequent protein expression affect disease progression and metastasis, drug resistance, and recurrence is of great interest in cancer research. In this regard, examining expression and activity of proteins, such as those with cytoprotective ability that are overexpressed in cancer cells, in addition to cell phenotype (i.e., stem-like, epithelial, mesenchymal, or mixed), are two ways to evaluate genetic and epigenetic changes. Moreover, determining the impact that cytoprotective proteins and cell phenotype have on tumor formation would be beneficial to clinicians and drug developers, as this would provide suitable targets for diagnostic testing and anti-cancer therapies. One such cytoprotective protein is human NAD(P)H:quinone oxidoreductase-1 (NQO1), due to its overexpression in diseased tissues. To this end, the goal of this research is to determine if the expression and activity of NQO1 and cell phenotype in human tumor-derived ovarian cancer cell lines influences in vitro spheroid formation. Therefore, in this work will be detailed, characterization of four ovarian cell lines as a function of (1) NQO1 activity and expression in two-dimensional monolayers in addition to proliferative ability; (2) spheroid formation under anchorage-independent culture conditions and subsequent NQO1 expression and activity in said spheroids; and (3) the phenotype as determined from presence of cancer stem cell markers and epithelial-to-mesenchymal transition in monolayer and spheroid culture.

Committee Chair

McCarley, Robin L.

DOI

10.31390/gradschool_dissertations.4968

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