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Insulin-like growth factor binding protein 2
enhances glioblastoma invasion by activating invasion-enhancing genes
Wang H, Wang H, Shen W, Huang H, Hu L, Ramdas L, Zhou YH, Liao WS, Fuller GN,
Zhang W
Department of Pathology, The University of Texas M. D. Anderson
Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
Comparison of gene expressing profiles between gliomas with different grades
revealed frequent overexpression of insulin-like growth factor binding protein 2
(IGFBP2) in glioblastoma (GBM), the most advanced stage of glioma.
To determine whether IGFBP2 is involved in the proliferative and invasive nature
of GBM, we established stable SNB19 GBM cell lines that overexpress
IGFBP2.
Although there was no marked difference in the cell growth between IGFBP2
overexpressing SNB19(BP2) lines when compared with the control cells, these
clones showed significantly increased invasive rates when compared with the
parental or vector transfected SNB19 cells.
Total RNAs from controls and SNB19(BP2) clones were used for microarray analysis
to detect IGFBP2-mediated alterations in gene expression.
When compared with parental or vector-transfected control cells, SNB19(BP2)
cells consistently showed 3-5-fold increase in the expression of matrix
metalloproteinase-2 (MMP-2) as well as other invasion related genes.
Increased MMP-2 expression in SNB19(BP2) cells was subsequently confirmed by
real time reverse-transcription PCR, Western blotting, and gelatin
zymography.
Furthermore, consistent with increased MMP-2 expression in SNB19(BP2) cells,
transient transfection of a MMP-2 promoter/luciferase reporter also resulted in
3-6-fold higher luciferase activity in SNB19(BP2) cells than in parental or
vector-transfected control cells.
Finally, tissue microarray analysis of 68 GBM tissue specimens showed a
significant correlation between the overexpression of IGFBP2 and elevated MMP-2
expression.
Taken together, our data provide evidence that IGFBP2 contributes to glioma
progression in part by enhancing MMP-2 gene transcription and in turn tumor cell
invasion.
PMID: 12907597 [PubMed - in process]
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