Expression, enzymatic activity, and inhibition of MMP-3 in C6-13 rat glioma cells

Poole, Alisha

Brandon, Manitoba

Brandon University, Faculty of Science

2018

2018

xvi, 105 pages : color illustrations

thesis

Includes bibliographical references (pages 90-101).
"In partial fulfillment of the requirements for the degree of Master of Science, Evironmental and Life Sciences."

English

Glioblastoma multiforme is the most aggressive form of brain cancer due to high rates of reoccurrence. Although >95% of a tumor can be removed with surgery, the invasiveness of gliomas frequently leads to the formation of tumors at secondary sites. The invasiveness of gliomas is in part due to their ability to secrete proteolytic enzymes, including members of the matrix metalloproteinase (MMP) family, that are involved with the remodeling of the extracellular matrix. In this study, MMP-3 expression and activity was found to be upregulated in C6-13 rat glioma cells that exogenously express the promigratory protein Cx43. Based on these findings, a panel of synthesized inhibitors were proposed and benchmarked against ilomastat, a known inhibitor of MMP-3. Binding ability of inhibitors to the MMP-3 active site was performed using in silico molecular docking. Ilomastat was chosen for further activity studies, in which MMP-3 was significantly inhibited. Findings presented in this thesis indicate that MMP-3 activity is upregulate in C6-13 rat glioma cells and can be significantly inhibited. MMP-3 inhibition may contribute to decreasing invasive potential of glioma cells.

Glioblastoma multiforme--Genetic aspects
Cancer invasiveness
Extracellular matrix proteins
Metalloproteinases
Protein binding
Genetic regulation

Brandon University.
Faculty of Science