SCIENCE SIGNALING

Lateral Receptor Transfer

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Science  23 May 2008:
Vol. 320, Issue 5879, pp. 989
DOI: 10.1126/science.320.5879.989c

Although many malignant gliomas display EGFRvIII, an oncogenic mutant form of the epidermal growth factor receptor (EGFR), the mutant receptor may be expressed only by a subset of cells in the tumor. Al-Nedawi et al. found that a human glioma cell line (U373) transfected with EGFRvIII (U373vIII) produced more membrane-derived microvesicles than did the parent cell line. The U373vIII cell-derived microvesicles contained EGFRvIII, as well as the lipid raft marker flotillin-1. Unlike U373 cells, U373vIII cells formed subcutaneous tumors when injected into immunodeficient mice, and these tumors released EGFRvIII-containing microvesicles into the circulatory system. U373 cells that had been exposed to EGFRvIII-containing microvesicles showed increased phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2). Pharmacological treatment to inhibit signaling by EGFR-family receptors attenuated this increase in ERK1/2 phosphorylation, as did treatment with annexin V (to prevent microvesicle uptake). EGFRvIII-containing microvesicles also stimulated other downstream events: release of vascular endothelial growth factor, levels of the anti-apoptotic protein Bcl-xL, and the ability of U373 cells to grow in soft agar (indicative of malignant transformation). The authors conclude that membrane microvesicles provide a pathway for transfer of the transformed phenotype. — EMA

Nat. Cell Biol. 10, 619 (2008).

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