Zhou Yan, Zhang Jing, Liu Qiang, Bell Robert, Muruve Daniel A, Forsyth Peter, Arcellana-Panlilio Mayi, Robbins Stephen, Yong V Wee
Department of Oncology, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
Carcinogenesis. 2005 Dec;26(12):2058-68. doi: 10.1093/carcin/bgi182. Epub 2005 Jul 20.
The chemokine GRO-alpha (CXCL1) has been found to mediate the proliferation of glia progenitor cells during neural development. As malignant gliomas are thought to arise from glia progenitors or their differentiated counterparts, astrocytes or oligodendrocytes, we have investigated whether GRO-alpha regulates the tumor characteristics of glioma cells. We found first that resected glioma specimens were strongly immunoreactive for GRO-alpha expression in cells with the morphology of tumor cells. In culture, the U251 glioma line transfected to overexpress GRO-alpha had elevated levels of motility and invasiveness. GRO-alpha transfectants increased their expression of several proteins associated with migratory behavior, including matrix metalloproteinase-2, beta1-integrin and SPARC. The implantation of GRO-alpha glioma clones into the brain of nude mice caused the early demise of mice and this was associated with the formation of larger intracerebral tumors when compared with mice implanted with vector control lines. These results implicate GRO-alpha in gliomas and suggest that the dysregulation of a glia proliferative factor contributes to tumorigenesis. Targeting GRO-alpha may be a useful therapeutic tool to control brain tumor biology.
趋化因子GRO-α（CXCL1）已被发现可在神经发育过程中介导神经胶质祖细胞的增殖。由于恶性胶质瘤被认为起源于神经胶质祖细胞或其分化后的对应细胞，即星形胶质细胞或少突胶质细胞，因此我们研究了GRO-α是否调节胶质瘤细胞的肿瘤特性。我们首先发现，切除的胶质瘤标本中，具有肿瘤细胞形态的细胞对GRO-α表达呈强免疫反应性。在培养中，转染以过表达GRO-α的U251胶质瘤细胞系的运动性和侵袭性水平升高。GRO-α转染细胞增加了几种与迁移行为相关蛋白的表达，包括基质金属蛋白酶-2、β1整合素和富含半胱氨酸的酸性分泌蛋白。将GRO-α胶质瘤克隆植入裸鼠脑内导致小鼠早期死亡，与植入载体对照细胞系的小鼠相比，这与更大的脑内肿瘤形成有关。这些结果表明GRO-α与胶质瘤有关，并提示神经胶质增殖因子的失调有助于肿瘤发生。靶向GRO-α可能是控制脑肿瘤生物学特性的一种有用治疗手段。
