title: Low Concentration Microenvironments Enhance the Migration of Neonatal Cells of Glial Lineage.
abstract: Glial tumors have demonstrated abilities to sustain growthviarecruitment 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 cuesviamigration 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.
authors.affiliation: Department of Biomedical Engineering, The City College of The City University of New York (CCNY), 160 Convent Avenue, Steinman Hall Room 403D, New York, NY 10031, USA ; Department of Biochemistry, The City Graduate Center of The City University of New York (CCNY), 365 Fifth Avenue, New York, NY 10016, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Able
authors.forename: Celestin
authors.initials: C
authors.lastname: Ngnabeuye
authors.forename: Cade
authors.initials: C
authors.lastname: Beck
authors.forename: Eric C
authors.initials: EC
authors.lastname: Holland
authors.forename: Maribel
authors.initials: M
authors.lastname: Vazquez
keywords: Chemotaxis; Concentration gradients; Glial progenitors; Glioma; Microfluidics; RCAS tv-a; TGF-α