System development for microquantitative molecular analyses ofglioma stem cells

点击翻译按钮获取中文摘要

Glioma initiating cells (GICs) are considered responsible for thetherapeutic resistance and recurrence of malignant glioma. T o clarify the molecularmechanism of GIC differentiation, we established GIC clones which differentiate intomalignant gliomas, and subjected to DNA microarray/iTRAQ based integrated proteomics(iPEACH). GO analysis revealed that the expression of cell adhesion molecules, includingintegrin subfamilies and ECMs, was significantly upregulated during serum-induced GICdifferentiation. This process, also accompanied by the upregulation of MAPK/PI3K signals,was dramatically accelerated by these ECMs and suppressed by integrin inhibitors such asRGD which also inhibited GIC proliferation, and raised their sensitivity against TMZ.Combination treatments of TMZ and RGD inhibit glioma progression and lead the longersurvival of mouse intracranial GIC xenograft model. GICs induce/secrete ECMs to developmicroenvironments, namely differentiation niches that further stimulate GICdifferentiation and proliferation via the integrin recognition motif RGD. This studyprovides a new perspective for developing therapeutic strategies against the early onset ofGIC-associated glioma.