Soluble Urokinase Receptor Is Released Selectively by Glioblastoma Cells That Express Epidermal Growth Factor Receptor Variant III and Promotes Tumor Cell Migration and Invasion

摘要: Genomic heterogeneity is characteristic of glioblastoma (GBM). In many GBMs, the EGF receptor gene (EGFR) amplified and may be truncated to generate a constitutively active form called EGFRvIII. EGFR amplification EGFRvIII are associated with GBM progression, even when only small fraction tumor cells express this study, we show that EGFRvIII-positive significantly increased levels cellular urokinase (uPAR) release amounts soluble uPAR (suPAR). When mice were xenografted human EGFRvIII-expressing cells, tumor-derived suPAR was detected in plasma, level compared plasma samples from control EGFRvIII-negative cells. also patients GBMs. Purified biologically added cultures activating cell signaling promoting migration invasion. did not stimulate or probably because already substantially activated these The activities replicated by conditioned medium (CM) CM preincubated uPAR-neutralizing antibody expression silenced used prepare CM, activity attenuated. These results suggest function as an important paracrine factor inducing aggressive phenotype EGFRvIII-negative.