The phosphorylation of ephrin-B2 ligand promotes glioma cell migration and invasion.

摘要: To reveal molecular drivers of glioma invasion, two distinct glioblastoma (GBM) cell phenotypes (invading cells and tumor core cells) were collected from 19 GBM specimens using laser capture microdissection. Isolated RNA underwent whole human genome expression profiling to identify differentially expressed genes. Pathway enrichment analysis highlighted the bidirectional receptor/ligand tyrosine kinase system, EphB/ephrin-B, as most tightly linked system invading phenotype. Clinical relevance ephrin-B genes was confirmed in a clinically annotated data set 195 brain biopsy specimens. Levels ephrin-B1 -B2 mRNA significantly higher (n = 82) than normal 24). Kaplan-Meier demonstrated ephrin-B2, but not ephrin-B1, levels associated with short term survival malignant astrocytomas 97, p 0.016). In specimens, production phosphorylation ephrin-B2 high GBM. Immunohistochemistry localization primarily brain. A highly invasive line, U87, compared relatively less lines. Treatment EphB2/Fc chimera further enhanced migration invasion U87 cells, whereas treatment an blocking antibody slowed invasion. Forced U251 line stimulated vitro ex vivo, concomitant ephrin-B2. These results demonstrate that is strong predictor short-term plays critical role rendering this signaling pathway potential therapeutic target.