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Updated: May 31, 2026
Impedance-based Real-time Measurement of Cancer Cell Migration and Invasion
Published on: April 2, 2020
Indirubins decrease glioma invasion by blocking migratory phenotypes in both the tumor and stromal endothelial cell
Shanté P Williams1, Michal O Nowicki, Fang Liu
1Dardinger Laboratory for Neuro-oncology and Neurosciences, Department of Neurological Surgery, The Ohio State University Medical Center and James Comprehensive Cancer Center, Columbus, Ohio 43210, USA.
Abstract:
Invasion and proliferation in neoplasia require the cooperation of tumor cell and endothelial compartments. Glycogen synthase kinase-3 (GSK-3) is increasingly recognized as a major contributor to signaling pathways that modulate invasion and proliferation. Here we show that GSK-3 inhibitors of the indirubin family reduce invasion of glioma cells and glioma-initiating cell-enriched neurospheres both in vitro and in vivo, and we show that β-catenin signaling plays an important role in mediating these effects. Indirubins improved survival in glioma-bearing mice in which a substantial decrease in blood vessel density was seen in treated animals. In addition, indirubins blocked migration of endothelial cells, suggesting that anti-invasive glioma therapy with GSK-3 inhibitors in vivo not only inhibits invasion of tumor cells, but blocks migration of endothelial cells, which is also required for tumor angiogenesis. Overall, our findings suggest that indirubin inhibition of GSK-3 offers a novel treatment paradigm to target 2 of the most important interacting cellular compartments in heterotypic models of cancer.
Insights
Indirubin GSK-3 inhibitors reduce glioma invasion and proliferation by targeting tumor and endothelial cells. These compounds improved survival in mice by blocking tumor angiogenesis and cell migration.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Neoplastic invasion and proliferation involve complex interactions between tumor and endothelial cells.
- Glycogen synthase kinase-3 (GSK-3) is a key signaling molecule implicated in cancer cell invasion and proliferation.
- Targeting GSK-3 presents a potential therapeutic strategy for various cancers.
Purpose of the Study:
- To investigate the efficacy of GSK-3 inhibitors, specifically indirubins, in combating glioma.
- To elucidate the role of beta-catenin signaling in indirubin-mediated anti-glioma effects.
- To assess the impact of indirubins on tumor angiogenesis and endothelial cell migration in vivo.
Main Methods:
- In vitro and in vivo experiments using glioma cells and neurospheres.
- Administration of GSK-3 inhibitors (indirubins) to glioma models.
- Assessment of cell invasion, proliferation, beta-catenin signaling, and tumor angiogenesis.
- Evaluation of endothelial cell migration and survival rates in glioma-bearing mice.
Main Results:
- Indirubin GSK-3 inhibitors significantly reduced glioma cell and neurosphere invasion.
- Beta-catenin signaling was identified as a crucial mediator of indirubin's anti-invasive effects.
- Indirubins improved survival in glioma-bearing mice, accompanied by decreased blood vessel density.
- Indirubins inhibited endothelial cell migration, suggesting a dual anti-angiogenic and anti-invasive mechanism.
Conclusions:
- Indirubin inhibition of GSK-3 offers a novel therapeutic approach for glioma.
- This strategy targets both tumor cells and the tumor microenvironment, including endothelial cells.
- GSK-3 inhibitors represent a promising treatment paradigm for cancers involving complex cellular interactions.
