CBIO-43ROLE OF BASIGIN-3 IN MMP EXPRESSION IN GBM

Abstract

Glioblastoma multiforme (GBM) is one of the most aggressive forms of brain tumor. With the current standard of care, the five year survival rate for GBM patients is less than 3%. An understanding of the molecular mechanisms promoting growth and survival of GBMs may result in novel treatments for this disease. A recent report indicated that the expression of the protein Basigin is a significant prognostic indicator for tumor grade in GBM patients, with tumors expressing highest levels of basigin protein correlating with the most aggressive tumors (Yang 2013). The Basigin gene family contains four isoforms, with Basigin-2 the predominant isoform expressed in both normal and diseased tissue. In 2011, Liao et al, suggested that Basigin-3 interacts with Basigin-2 in Human Hepatocellular Carcinoma (HHC), leading to decreased tumor growth and invasion. Because the Basigin-2 protein (CD-147/EMMPRIN) is a known inducer of matrix metalloproteinase (MMP) the inhibition of Basigin-2 through its interaction with Basigin-3 should decrease both tumor growth and MMP expression. To test this hypothesis, a recombinant Basigin-3/mKate2 fluorescent protein fusion was overexpressed in a GBM cell line (LN229), and RT-qPCR was used to measure MMP gene expression. Confocal microscopy and western blot analysis confirmed the over-expression of Basigin-3 in the transfected populations. However, the overexpression of Basigin-3 did not reduce the expression of MMP-1, MMP-2, and MMP-3. Our data suggest that the role of Basigin-3 in GBM may be different from what was shown in HHCs. Currently, we are performing FRET analysis between Basigin-2 and Basigin-3 to confirm their interaction in our model.