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Author

Samantha Weed

Date of Award

4-21-2004

Document Type

Restricted Thesis: Campus only access

Degree Name

Bachelor of Science

Department

Biology

First Advisor

Dr. Valerie Kish

Abstract

Gliomas are the most common type of intracranial tumors in humans (Russell and Rubenstein, 1989). The low survival rate of glioma patients necessitates a greater understanding of the mechanisms that underlie invasive gliomas. Matrix metalloproteinases (MMPs) are the largest group of enzymes capable of degrading the extracellular matrix and are strongly implicated in the invasive properties of gliomas (Uhm et al., 1997). The signaling pathway that regulates the production and activity of these enzymes is unclear, and discovering this pathway is a main target in anti-invasive therapy. Among the MMP family, MMP-2 and MMP-9 have been identified as being primarily responsible for the invasiveness of glioblastomas. Preliminary findings suggest that the epidermal growth factor (EGF) binds to its receptor (EGFR) on the cell's surface, initiating many different signal cascades, one of which leads to the production of MMP-2 and MMP-9 (Uhm et al., 1997). Prior research has shown that Concanavalin A (ConA) is also involved in inducing the activation of MMP-2. ConA is a plant lectin and nonspecific epidermal cell mitogen that is widely used to stimulate production of cellular products. ConA affects the expression of mRNA for MT1-MMP, a recently discovered cell surface-associated MMP that induces the activation of MMP-2. We have examined the effect of EGF and ConA on levels of MMP-2 and MMP-9 activity using human glioblastoma cell lines U87 and LNZ-308. U87 cell lines contain the wild type p53 gene, while LNZ cell lines contain a null mutation for the p53 gene. p53, a tumor suppressor protein, acts as a transcription factor for the MMP-2 gene. Our results indicate that LNZ-308 glioma cell lines do not secrete MMP-2. In the U87 glioma cell lines, the overall production and secretion of MMP-2 increases with increasing EGF concentrations, consistent with previous research findings (Rooprai et al, 2000; Uhm et al., 1997). However, the overall production and secretion of MMP-2 decreased with increasing ConA concentrations, which is inconsistent with the literature findings.

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