Abstract:
:Uncontrolled growth and diffused invasion are major causes of mortality in patients with malignant gliomas. Nodal has been shown to have a central role in the tumorigenic signaling pathways of malignant melanoma. In this study, we show that grade IV human glioma cell lines expressed different levels of Nodal, paralleled to the potential for cell invasiveness. Treatment of glioma cell lines with recombinant Nodal (rNodal) increased matrix metalloproteinase 2 (MMP-2) secretion and cell invasiveness. The ectopic expression of Nodal in GBM glioma cells that expressed Nodal at low level resulted in increased MMP-2 secretion, enhanced cell invasiveness, raised cell proliferation rates in vitro, increased tumor growth in vivo, and was associated with poor survival in a mice xenograft model. In contrast, the knockdown of Nodal expression in U87MG glioma cells with high Nodal expression level had reduced MMP-2 secretion, less cell invasiveness, lower tumor growth in vivo and longer lifespan in mice with U87MG/shNodal cell xenografts. In addition, Nodal knockdown promoted the reversion of malignant glioma cells toward a differentiated astrocytic phenotype. Furthermore, our data support the notion that Nodal may regulate glioma progression through the induction of the leukemia inhibitory factor (LIF) and Cripto-1 through activated Smad.
journal_name
Oncogenejournal_title
Oncogeneauthors
Lee CC,Jan HJ,Lai JH,Ma HI,Hueng DY,Lee YC,Cheng YY,Liu LW,Wei HW,Lee HMdoi
10.1038/onc.2010.55subject
Has Abstractpub_date
2010-05-27 00:00:00pages
3110-23issue
21eissn
0950-9232issn
1476-5594pii
onc201055journal_volume
29pub_type
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