Investigation of Surface Glycans on Glioblastoma multiforme and Its Stem Cells
Date Issued
2014
Date
2014
Author(s)
Lou, Yi-Wei
Abstract
Glioblastoma multiforme (GBM), the grade IV astrocytoma, is the most common and aggressive brain tumor in adults. Despite advances in medical managements, the survival rate of GBM patients remains poor, suggesting that identification of GBM-specific targets for therapeutic development is urgently needed. Analysis of several glycan antigens on GBM cell lines revealed that 12 out of 17 GBM cell lines were positive for stage-specific embryonic antigen-4 (SSEA-4), and the identity of SSEA-4 was confirmed by high performance thin-layer chromatography immunostaining and mass spectrometry. Immunohistochemical staining confirmed that 38/55 (69%) of human GBM specimens, but not normal brain tissue, were SSEA-4-positive, and correlated with high-grade astrocytoma. MC813-70, an SSEA-4 specific monoclonal antibody, was found to induce complement-dependent cytotoxicity against SSEA-4hi GBM cell lines in vitro, and suppressed GBM tumor growth in mice. Since SSEA-4 is expressed on GBM and many other types of cancers, but not on normal cells, it could be a target for development of therapeutic antibodies and vaccines. On the other hand, we successfully generated a population of GBM cells with higher stemness and tumorigenicity. In order to discover the specific markers expressed on GBM stem cells, we utilized a panel of glycan-related antibodies to profile the expression of glycan epitopes, including glycoproteins or glycolipids. Among these glycans, the expression of GD2 was found to be elevated on stem-like cell population. Further study would illustrate the relationship between GD2 and GBM stem cells.
Subjects
多形性神經膠母細胞瘤
階段特異性胚胎抗原-4
單株抗體
醣脂
腫瘤幹細胞
神經節苷脂
標靶治療
腫瘤相關抗原
SDGs
Type
thesis
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