Nodal promotes growth and invasion in human gliomas
Journal
Oncogene
Journal Volume
29
Journal Issue
21
Pages
3110-3123
Date Issued
2010
Author(s)
Lee, C.-C.
Jan, H.-J.
Lai, J.-H.
Ma, H.-I.
Hueng, D.-Y.
Gladys Lee, Y.-C.
Cheng, Y.-Y.
Liu, L.-W.
Lee, H.-M.
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. ? 2010 Macmillan Publishers Limited All rights reserved.
Subjects
Glioma; Invasion; MMP-2; Nodal
SDGs
Other Subjects
cripto 1 protein; gelatinase A; growth factor; leukemia inhibitory factor; protein Nodal; recombinant protein; Smad protein; unclassified drug; article; astrocyte; cancer grading; cancer growth; cancer invasion; cancer survival; cell differentiation; cell proliferation; disease association; gene expression regulation; glioma; glioma cell; human; in vitro study; in vivo study; lifespan; mouse; nonhuman; phenotype; priority journal; protein secretion; xenograft; Animals; Cell Division; Cell Line, Tumor; Central Nervous System Neoplasms; Disease Progression; Epidermal Growth Factor; Gene Expression Regulation, Neoplastic; Gene Knockout Techniques; Glioma; Humans; Intracellular Signaling Peptides and Proteins; Leukemia Inhibitory Factor; Matrix Metalloproteinase 2; Membrane Glycoproteins; Membrane Proteins; Mice; Neoplasm Invasiveness; Neoplasm Proteins; Recombinant Proteins; Smad Proteins; Tissue Inhibitor of Metalloproteinase-2; Transfection; Mus
Type
journal article