부산대학교 도서관

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor, for which an effective pharmacotherapy remains unavailable. Several targeted therapies and chemotherapeutic agents have failed to increase survival or enhance patient outcomes in GBM. In order to understand this pathology, the aim of our study was to evaluate the influence induced by different micro-media on the expression of some biomarkers as fundamental aspects of niche influence on cells fate. Materials and method. The cell lines were obtained from glioblastoma multiforme through mechanically dissociation and maintenance in two different media: DMEM supplemented with epidermal growth factor (EGF), B27, and N2 (STON-BEN line), or DMEM supplemented with fetal bovine serum (FBS) (STONa line). On DMEM supplemented with EGF, B27 and N2, STON formed neurospheres, while in the presence of serum, the cells became adherent, forming monolayer. The specific characteristics of cells cultured in different media were evaluated using Protein Profiler Array and real time PCR. Results. In STON-BEN, the line that, accordingly to our previously in vivo studies, has a high metastatic potential and produce very aggressive tumors, the anti-angiogenic ADAMTS-1 protein was less expressed, whereas its antagonist, the pro-angiogenic protein TIMP, presented a very high level of expression. Also, in BEN culture media, higher levels of angiogenin (an activator of genes that inhibit apoptosis, supporting the tumor process by proliferation, invasion and migration) and vascular endothelial growth factor (VEGF; a great stimulator of vasculogenesis and angiogenesis) were observed, as well as PDGF-AA, insulin-like growth factor-binding protein (IGFBP) etc. On the other hand, STONa line showed slightly increased levels of endotelin-1, trombospondin-1, endoglin CD105, angiopoietin, endostatin etc. Conclusions. Our results demonstrate that niche microenvironment influenced the cell fate and complicated signaling paths, and the multitude of processes occur simultaneously in the tumor cells. Some established biomarkers could represent potential targets for a more effective treatment of aggressive forms, but further studies are needed. [ABSTRACT FROM AUTHOR]