Institute of Neurology, Medical University of Vienna, Vienna, Austria.
J Neurooncol. 2010 Dec;100(3):339-43. doi: 10.1007/s11060-010-0195-8. Epub 2010 May 9.
Signal transducer and activator of transcription protein 3 (STAT3) is a regulator of central nervous system (CNS) development and a promising therapeutic target in human cancers. Activation of STAT3 promotes oncogenesis in a variety of tissues, but knowledge of its role in glioblastoma is still limited. Recent results indicate that STAT3 acts as a tumor suppressor or an oncogene depending upon the genetic background of the tumor. Here we immunohistochemically assessed Y705-phosphorylated STAT3 (pY705-STAT3) in formalin-fixed, paraffin-embedded specimens of 111 patients with supratentorial glioblastomas and 25 patients with supratentorial grade III gliomas. We found that glioblastoma patients with high or very high numbers of pY705-STAT3-positive tumor cells had significantly shorter overall survival than those with no or low numbers (P = 0.001, Cox regression). Interestingly the proportion of grade III glioma cases with high or very high numbers of pY705-STAT3-positive tumor cells was similar to that in glioblastoma. Our findings provide evidence that activation of STAT3 by Y705 phosphorylation is linked with clinically more aggressive behavior in glioblastomas, but is most likely not associated with tumor progression of grade III gliomas. In sum, our results suggest that STAT3 inhibition should be considered as a therapeutic approach in malignant gliomas.
信号转导子和转录激活子蛋白 3（STAT3）是中枢神经系统（CNS）发育的调节剂，也是人类癌症中很有前途的治疗靶点。STAT3 的激活促进了多种组织的肿瘤发生，但人们对其在胶质母细胞瘤中的作用仍知之甚少。最近的结果表明，STAT3 根据肿瘤的遗传背景，作为肿瘤抑制因子或癌基因发挥作用。在这里，我们通过免疫组织化学方法检测了 111 例幕上胶质母细胞瘤和 25 例幕上 III 级胶质瘤患者福尔马林固定、石蜡包埋标本中 Y705 磷酸化的 STAT3（pY705-STAT3）。我们发现，pY705-STAT3 阳性肿瘤细胞数量高或非常高的胶质母细胞瘤患者的总生存期明显短于 pY705-STAT3 阳性肿瘤细胞数量低或无的患者（P = 0.001，Cox 回归）。有趣的是，III 级胶质瘤病例中 pY705-STAT3 阳性肿瘤细胞数量高或非常高的比例与胶质母细胞瘤相似。我们的研究结果表明，Y705 磷酸化激活 STAT3 与胶质母细胞瘤中更具侵袭性的临床行为有关，但与 III 级胶质瘤的肿瘤进展最可能无关。总之，我们的研究结果表明，STAT3 抑制应被视为恶性神经胶质瘤的一种治疗方法。
