高血管生成是胶质母细胞瘤（GBM）的典型特征，是最具侵略性的脑肿瘤。我们已经报道了脱氢醛酸脱氢酶1A3（ALDH1A3）在GBM患者的增殖血管中的表达。我们假设ALDH1A3可能在GBM中起到促血管生成的作用。两种GBM细胞系被逆转录病毒转导分别为ALDH1A3（ox）和空载体（ev）。在间接和直接共培养内皮细胞（ECs）与oxGBM细胞（oxGBMs）以及体内血管生成模型中研究了血管生成表型。在oxGBMs中进行血管生成阵列分析。RT2-PCR、Western blot和双免疫荧光染色用于确认从阵列中鉴定的靶点的表达。在ECs的间接和直接共培养以及体内观察到显著活化的血管生成表型。ALDH1A3过表达（oxALDH1A3）导致PAI-1和IL-8 mRNA和蛋白质的显著上调，并随之增加了这两种蛋白质的释放。此外，oxALDH1A3诱导的血管生成通过PAI-1和IL-8受体CXCR1/2的特定抑制剂治疗被废弃。本研究将ALDH1A3定义为一种新的血管生成促进剂。GBM细胞中的oxALDH1A3通过来源上调的PAI-1和IL-8刺激ECs的血管生成，提示ALDH1A3-PAI-1/IL-8作为未来GBM抗血管生成疗法的新型信号传导。

Hyper-angiogenesis is a typical feature of glioblastoma (GBM), the most aggressive brain tumor. We have reported the expression of aldehyde dehydrogenase 1A3 (ALDH1A3) in proliferating vasculature in GBM patients. We hypothesized that ALDH1A3 may act as an angiogenesis promoter in GBM. Two GBM cell lines were lentivirally transduced with either ALDH1A3 (ox) or an empty vector (ev). The angiogenesis phenotype was studied in indirect and direct co-culture of endothelial cells (ECs) with oxGBM cells (oxGBMs) and in an angiogenesis model in vivo. Angiogenesis array was performed in oxGBMs. RT2-PCR, Western blot, and double-immunofluorescence staining were performed to confirm the expression of targets identified from the array. A significantly activated angiogenesis phenotype was observed in ECs indirectly and directly co-cultured with oxGBMs and in vivo. Overexpression of ALDH1A3 (oxALDH1A3) led to a marked upregulation of PAI-1 and IL-8 mRNA and protein and a consequential increased release of both proteins. Moreover, oxALDH1A3-induced angiogenesis was abolished by the treatment of the specific inhibitors, respectively, of PAI-1 and IL-8 receptors, CXCR1/2. This study defined ALDH1A3 as a novel angiogenesis promoter. oxALDH1A3 in GBM cells stimulated EC angiogenesis via paracrine upregulation of PAI-1 and IL-8, suggesting ALDH1A3-PAI-1/IL-8 as a novel signaling for future anti-angiogenesis therapy in GBM.