Analysis of cross talk between human glioma cells and endothelial cells, and molecular targeted therapy

恶性脑肿瘤，如胶质母细胞瘤，表现出明显的血管生成，但肿瘤细胞生长在缺氧条件下没有足够的血液供应。实体瘤对放化疗敏感性低，预后差，易复发。低氧诱导因子1 α（hypoxia-induciblefactor 1 α，HIF 1 α）是一种在低氧条件下发挥作用的转录因子。近年来，HIF 1 α诱导基质细胞衍生因子-1（SDF-1）及其受体CXCR 4基因表达。SDF-1募集CXCR 4阳性干细胞和祖细胞，修复缺氧损伤的组织。这些反应是肿瘤在缺氧条件下生存所必需的。此外，这种缺氧微环境调节肿瘤特性。因此，我们分析了人脑胶质瘤细胞与内皮细胞之间的相互作用，并对分子靶向治疗进行了研究。本研究的目的是在低氧条件下对干细胞进行控制，并将其应用于未来的医学治疗。

Malignant brain tumor, such as glioblastoma, showed prominent angiogenesis, however tumor cells were growing without sufficient blood supply under hypoxic condition. The solid tumor, which showed the low sensitivity to chemoradiotherapy, led to a less favorable outcome, recurrence and poor prognosis. We previously have focused on hypoxia-inducible factor1α (HIF1α), transcription factor which worked under hypoxic condition. Recently, HIF1α induced the expression of stromal cell-derived factor-1(SDF-1) and its receptor, CXCR4 gene. SDF-1 recruits CXCR4-positive stem cells and progenitor cell, and repairs the tissue damaged by hypoxia. These reactions are necessary for the tumors to survive under hypoxic condition. In addition, such hypoxic microenvironment regulates the tumor characteristics. Therefore, we analyzed the cross talk between human glioma cells and endothelial cells, and investigated the molecular targeted therapy. We aimed to control the stem cell under hypoxic condition and apply to the future medical treatment.