Role of MEK-ERK signaling mediated adhesion of glioma cells to extra-cellular matrix: Possible implication on migration and proliferation

BACKGROUND: Glioblastoma represents the most common primary brain tumor with a worst prognosis despite developments in neurosurgery and chemoradiotherapy. Detachment of the cells from the primary tumor tissue is a prerequisite for their dispersion and spreading. Initial and incessant dispersal of tumor cells from the primary tumor tissue renders GBM refractory to comprehensive surgical removal and increases the chance of recurrence and poorer prognosis. PURPOSES: The current study was designed to investigate the effect of inhibition of MEK-ERK1/2 signaling by PD98059 and U0126 on the growth and migration of glioma cells as well as their adhesion to extracellular matrix. METHODS: MEK-ERK1/2 signaling in U87-MG cells was inhibited by PD98059 and U0126. Migration, proliferation and adhesion were analyzed by scratch-wound assay, MTT assay, cell adhesion assay respectively. RESULTS: PD98059 and U0126 significantly not only reduced the proliferation of glioma cells and attenuated their migration but also increased their adhesion to gelatin of extracellular matrix. CONCLUSION: This study provides the evidence that inhibition of MEK-ERK1/2 signaling enhances the adhesion of glioma cells to gelatin/collagen component of ECM, and decreases the proliferation and migration of the glioma cells. We propose the possible rationale of association between ERK signaling and cell-cell adhesion molecules in glioma microenvironment which regulates the glioma initiation, growth and progression.