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Updated: Jun 14, 2026
Three-Dimensional (3D) Tumor Spheroid Invasion Assay
Published on: May 1, 2015
Nodal promotes growth and invasion in human gliomas
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.
Insights
Nodal signaling drives malignant glioma progression by increasing invasiveness and proliferation. Inhibiting Nodal in high-grade gliomas promotes cell differentiation and improves survival in preclinical models.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cancer Signaling
Background:
- Malignant gliomas are aggressive brain tumors characterized by uncontrolled growth and invasion.
- Nodal signaling is implicated in various cancers, including melanoma, but its role in gliomas is less understood.
Purpose of the Study:
- To investigate the role of Nodal in the progression of malignant gliomas.
- To determine if Nodal influences glioma cell invasiveness, proliferation, and differentiation.
Main Methods:
- Assessed Nodal expression levels in human glioma cell lines and correlated them with invasiveness.
- Treated glioma cells with recombinant Nodal (rNodal) and analyzed matrix metalloproteinase 2 (MMP-2) secretion and invasiveness.
- Utilized ectopic Nodal expression and Nodal knockdown (shNodal) in glioma cells.
- Evaluated tumor growth and survival in mice xenograft models.
- Investigated downstream signaling pathways involving leukemia inhibitory factor (LIF) and Cripto-1 via Smad.
Main Results:
- Nodal expression levels correlated with glioma cell invasiveness.
- rNodal treatment increased MMP-2 secretion and cell invasiveness.
- Ectopic Nodal expression enhanced proliferation, invasiveness, tumor growth, and reduced survival.
- Nodal knockdown reduced invasiveness, tumor growth, and prolonged survival.
- Nodal knockdown induced a reversion toward a differentiated astrocytic phenotype.
Conclusions:
- Nodal signaling is a key driver of malignant glioma progression.
- Nodal promotes glioma cell invasiveness and proliferation, potentially through LIF and Cripto-1.
- Targeting Nodal signaling may offer a therapeutic strategy for high-grade gliomas.
