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EGF as a New Therapeutic Target for Medulloblastoma Metastasis.

Cellular and molecular bioengineering (2015-11-26)
Jennifer Rico-Varela, Tanya Singh, Sean McCutcheon, Maribel Vazquez
ABSTRACT

Medulloblastoma (MB) is a malignant pediatric brain tumor known for its aggressive metastatic potential. Despite the well-documented migration of MB cells to other parts of the brain and spinal column, MB chemotaxis is poorly understood. Herein, we examined the in vitro migratory and cellular responses of MB-derived cells to external signaling of Epidermal Growth Factor (EGF), hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF-BB), and the stromal cell-derived factors 1-alpha (SDF-1). Experiments utilized transwell assays and immunocytochemistry to identify receptor activation in MB migration, and used a microfluidic platform to examine directionality, trajectory, and gradient-dependence of motile cells. Data illustrates that MB-derived cells respond strongly to EGF in a dosage and gradient-dependent manner with increased EGF-R activation, and show that high EGF gradient fields cause an increased number of cells to migrate longer directed distances. Our results provide evidence that EGF and its receptor play an important role than previously documented in MB chemotactic migration than previously documented and should be considered for developing migration-target therapies against MB metastasis.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Integrin αVβ3 Antibody, clone LM609, clone LM609, Chemicon®, from mouse
Sigma-Aldrich
Goat Anti-Rabbit IgG Antibody, FITC conjugate, 2 mg/mL, Chemicon®