Department of Neurological Surgery, Vanderbilt University Medical Center, T-4224, Medical Center North, Nashville, TN 37232, USA.
J Neurooncol. 2013 Jun;113(2):153-62. doi: 10.1007/s11060-013-1108-4. Epub 2013 Mar 14.
CXCR4, a cell surface chemokine receptor, mediates cellular dissemination, invasion, and proliferation in a wide range of cancers including gliomas. It is over-expressed in glioma progenitor cells, and its protein ligand, CXCL12, has been shown to mediate a specific proliferative response in these cells thereby implicating a role for CXCR4 in glioma initiation and renewal. Given the failure of currently employed therapies to meaningfully impact prognosis in patients with high-grade gliomas, the CXCR4-CXCL12 axis represents a novel biologically relevant mechanism that could be specifically targeted for therapy. From this perspective, this review summarizes the biological effects of CXCR4 activity and its implications for glioma pathogenesis. Ultimately, the development of effective treatment approaches for malignant glioma must be based on a rational mechanistic understanding of tumor cell biology. As such, this article presents such a framework with regard to the CXCR4 pathway in glioma thereby supporting the further investigation of CXCR4 as a therapeutic target in patients with this disease.
趋化因子受体 4（CXCR4）是一种细胞表面趋化因子受体，介导多种癌症（包括神经胶质瘤）中的细胞播散、侵袭和增殖。它在神经胶质瘤祖细胞中过表达，其蛋白配体 CXCL12 已被证明可在这些细胞中介导特定的增殖反应，从而表明 CXCR4 在神经胶质瘤的发生和更新中起作用。鉴于目前使用的治疗方法未能对高级别神经胶质瘤患者的预后产生明显影响，因此 CXCR4-CXCL12 轴代表一种新的具有生物学相关性的机制，可针对该机制进行特异性治疗。从这个角度来看，本综述总结了 CXCR4 活性的生物学效应及其对神经胶质瘤发病机制的影响。最终，恶性神经胶质瘤的有效治疗方法的开发必须基于对肿瘤细胞生物学的合理机制理解。因此，本文针对神经胶质瘤中的 CXCR4 途径提出了这样一个框架，从而支持进一步研究 CXCR4 作为该疾病患者的治疗靶点。
