Abstract 219: Glycosylation-dependent effect of CD109 on TGF-beta1 and EGF signaling in human glioblastoma cells

Abstract

Abstract CD109, a glycosylphosphatidylinositol-anchored cell surface glycoprotein, is a negative regulator of TGF-beta1 signaling, whose expression is predominantly detected in squamous cell carcinomas of esophagus, lung, uterus and oral cavity. In the Northern blot analysis using various human tumor cell lines, we found CD109 expression in cell lines derived from human glioblastomas, however, the significance of CD109 in glioblastoma cells has not yet been elucidated. Here, we present the glycosylation-dependent effect of CD109 on TGF-beta1 and EGF signaling in glioblastoma cells. SK-MG-1 cells overexpressing CD109 exhibited downregulation of Smad2 phosphorylation after TGF-beta1 stimulation and upregulation of EGFR and ERK1/2 phosphorylation after EGF stimulation, indicating that CD109 is involved in not only negative regulation of TGF-beta1 signaling but also positive regulation of EGF signaling. However, in other glioblastoma cell lines, U251MG and MG178, CD109 overexpression showed no significant effect on TGF-beta1 and EGF signaling. CD109 overexpression also enhanced cell proliferation and migration in SK-MG-1 cells, but not in the other two cells. Western blot analysis showed that molecular mass of CD109 of SK-MG-1 cells was a bit high compared with those of the other two cell lines, and deglycosylation analysis revealed enhanced glycosylation of CD109 in SK-MG-1 cells. TGF-beta1 signal in U251MG and MG178 was suppressed when the medium with hyperglycosylated soluble form of CD109 was used for TGF-beta1 stimulation. Our results suggest the glycosylation-dependent effect of CD109 on cell biology of glioblastoma cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 219. doi:1538-7445.AM2012-219