Department of Oncology and Hematology with Section Pneumology, Oncology Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Cancer Lett. 2012 Dec 30;326(2):161-7. doi: 10.1016/j.canlet.2012.08.002. Epub 2012 Aug 16.
3-Hydroxiglutaric acid (3-OH-GA) is a disease-specific metabolite that accumulates in tissues and body fluids of patients with Glutaric aciduria type I (GAI) and has been associated with vascular abnormalities in these kindreds. Here, we demonstrate that 3-OH-GA also affects the integrity of tumor vessels leading to tumor growth inhibition in a subcutaneous model of human glioblastoma multiforme (GBM). This effect correlated with a marked decrease of VE-Cadherin expression in endothelium of 3-OH-GA-treated tumors. Furthermore, in vitro observations indicated also a direct effect of 3-OH-GA in glioma cells that showed defective mitosis and significant proliferation inhibition. In summary, the GAI-specific metabolite 3-OH-GA significantly inhibited growth of GBM xenografts by affecting the structural integrity of tumor blood vessels and in addition by causing defective mitosis and proliferation inhibition of tumor cells.
3-羟基戊二酸（3-OH-GA）是一种特异性代谢产物，在 I 型戊二酸血症（GAI）患者的组织和体液中积累，并与这些家族的血管异常有关。在这里，我们证明 3-OH-GA 还会影响肿瘤血管的完整性，从而抑制人多形性胶质母细胞瘤（GBM）的皮下模型中的肿瘤生长。这种作用与肿瘤内皮中 VE-Cadherin 表达的明显减少相关。此外，体外观察还表明 3-OH-GA 对神经胶质瘤细胞有直接作用，导致有丝分裂缺陷和明显的增殖抑制。总之，GAI 特异性代谢产物 3-OH-GA 通过影响肿瘤血管的结构完整性，以及引起肿瘤细胞有丝分裂缺陷和增殖抑制，显著抑制 GBM 异种移植物的生长。
