Date of Award

8-2017

Degree Type

Thesis

Degree Name

Master of Science

Department

Biology

Program

Biology

First Advisor/Chairperson

Dr. Robert Belton

Second Advisor

Dr. Josh Sharp

Third Advisor

Dr. John Lawrence

Fourth Advisor

Dr. John Rebers

Abstract

Glioblastoma multiforme (GBM) is the most common malignant form of human brain cancer. GBM tumor cells overexpress the protein Basigin (Bsg) at the cell surface where it contributes to malignancy via stimulation of matrix metalloproteinase (MMP) expression in surrounding normal tissues, resulting in the degradation of the extracellular matrix (ECM) surrounding tumors, promoting remodeling of the tumor borders, stimulating growth. In work by Belton et al. (2008), human uterine endometrial cells treated with a recombinant form of human basigin possessing the extracellular domain of the Bsg protein (rBsg-ECD) showed activation of the Mitogen-Activated Protein Kinase (MAPK) signaling pathway proteins, ERK1/2. This effect was mediated by rBsg-ECD binding to the Basigin-2 (Bsg-2) at the cell surface. In this research, U87-MG human GBM cells were treated with purified rBsg-ECD protein to measure changes in the phosphorylation of the ERK1/2 proteins. The results indicate the presence of a signaling loop within GBM tumors where soluble Bsg protein stimulates signal transduction through Bsg-2 at the cell surface. rBsg-mediated ERK1/2 stimulation is inhibited by the antioxidant compound Resveratrol, suggesting that the signaling mechanism through Bsg-2 involves the Epidermal Growth Factor Receptor (EGFR). Taken together, these results indicate that soluble Basigin protein stimulates signaling events through the MAPK signaling pathway by binding to Bsg-2 on the surface of GBM cells.

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