Increased transforming growth factor-β2 in epidermal growth factor receptor variant III-positive glioblastoma

Abstract

To evaluate the influence of epidermal growth factor receptor variant III (EGFRvIII) expression on immune impairment associated with glioblastoma multiforme (GBM), the expression of transforming growth factor beta-2 (TGF-β2) and interleukin-10 (IL-10) were assessed in EGFRvIII-positive and negative GBM samples. In addition, the effects of EGFRvIII expression on U87.MG glioma cell proliferation and invasion as well as TGF-β2 and IL-10 levels were analyzed. GBM samples were obtained from 26 patients who underwent surgical resection. EGFRvIII expression was assessed immunohistochemically and using real-time reverse transcription polymerase chain reaction (RT-PCR), and TGF-β2 and IL-10 levels were determined using real-time RT-PCR. Proliferation and invasion of U87.MG and U87.MG.EGFRvIII glioma cells was assessed using the 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Matrigel invasion assays, respectively. Although upregulation of TGF-β2 mRNA expression was observed in EGFRvIII-positive patients, no differences in IL-10 expression levels were detected. A statistically significant increase in cell proliferation and invasion as well as TGF-β2 and IL-10 expression was observed in U87.MG.EGFRvIII cells as compared with U87.MG cells. Associations between EGFRvIII expression and upregulation of immunosuppressive cytokines were observed. EGFRvIII expression was also associated with increased cell proliferation and invasion. Understanding the immunobiology of EGFRvIII-positive GBM patients may assist in the development of novel targeted treatment strategies.