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Low Concentration Microenvironments Enhance the Migration of Neonatal Cells of Glial Lineage

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Abstract

Glial tumors have demonstrated abilities to sustain growth via recruitment of glial progenitor cells (GPCs), which is believed to be driven by chemotactic cues. Previous studies have illustrated that mouse GPCs of different genetic backgrounds are able to replicate the dispersion pattern seen in the human disease. How GPCs with genetic backgrounds transformed by tumor paracrine signaling respond to extracellular cues via migration is largely unexplored, and remains a limiting factor in utilizing GPCs as therapeutic targets. In this study, we utilized a microfluidic device to examine the chemotaxis of three genetically-altered mouse GPC populations towards tumor conditioned media, as well as towards three growth factors known to initiate the chemotaxis of cells excised from glial tumors: Hepatocyte Growth Factor (HGF), Platelet-Derived Growth Factor-BB (PDGF-BB), and Transforming Growth Factor-α (TGF-α). Our results illustrate that GPC types studied exhibited chemoattraction and chemorepulsion by different concentrations of the same ligand, as well as enhanced migration in the presence of ultra-low ligand concentrations within environments of high concentration gradient. These findings contribute towards our understanding of the causative and supportive roles that GPCs play in tumor growth and reoccurrence, and also point to GPCs as potential therapeutic targets for glioma treatment.

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Acknowledgments

This work was supported by the National Science Foundation (BES 0428573) and the National Institutes of Health (CAR21118255, GMR21 071702). The authors are thankful for the contributions made by Georgina Bermudez towards the total receptor western blot data and to Veronica Rotari towards the U87 cell line migration data. The authors thank Justin Perry for illustration of the μLane system schematic. The authors also like to thank Dr. Veronica Dudu and Dr. Robert Majeska for their technical discussions and recommendations.

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Able, R.A., Ngnabeuye, C., Beck, C. et al. Low Concentration Microenvironments Enhance the Migration of Neonatal Cells of Glial Lineage. Cel. Mol. Bioeng. 5, 128–142 (2012). https://doi.org/10.1007/s12195-012-0226-y

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