Zhou Yan, Larsen Peter H, Hao Chunhai, Yong V Wee
Departments of Oncology and Clinical Neurosciences, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada.
J Biol Chem. 2002 Dec 20;277(51):49481-7. doi: 10.1074/jbc.M206222200. Epub 2002 Oct 17.
Chemokines were described originally in the context of providing migrational cues for leukocytes. They are now known to have broader activities, including those that favor tumor growth. We addressed whether and which chemokines may be important promoters of the growth of the incurable brain neoplasm, malignant gliomas. Analyses of 16 human glioma lines for the expression of chemokine receptors belonging to the CXCR and CCR series revealed low to negligible levels of all receptors, with the exception of CXCR4 that was expressed by 13 of 16 lines. All six resected human glioma specimens showed similarly high CXCR4 expression. The CXCR4 on glioma lines is a signaling receptor in that its agonist, stromal cell-derived factor-1 (SDF-1; CXCL12), produced rapid phosphorylation of mitogen-activated protein kinases. Furthermore, SDF-1 induced the phosphorylation of Akt (protein kinase B), a kinase associated with survival, and prevented the apoptosis of glioma cells when serum was withdrawn from the culture medium. SDF-1 also mediated glioma chemotaxis, in accordance with this better known role of chemokines. We conclude that glioma cells express a predominant chemokine receptor, CXCR4, and that this functions to regulate survival in part through activating pathways such as Akt.
趋化因子最初被描述为为白细胞提供迁移线索。现在已知它们具有更广泛的活性，包括那些促进肿瘤生长的活性。我们研究了趋化因子是否以及哪些趋化因子可能是无法治愈的脑肿瘤——恶性胶质瘤生长的重要促进因子。对16个人类胶质瘤细胞系进行属于CXCR和CCR系列的趋化因子受体表达分析，结果显示除16个细胞系中有13个表达的CXCR4外，所有受体的表达水平都很低或可忽略不计。所有6个切除的人类胶质瘤标本都显示出同样高的CXCR4表达。胶质瘤细胞系上的CXCR4是一种信号受体，因为其激动剂基质细胞衍生因子-1（SDF-1；CXCL12）能使丝裂原活化蛋白激酶快速磷酸化。此外，SDF-1能诱导与存活相关的激酶Akt（蛋白激酶B）磷酸化，并在从培养基中撤除血清时防止胶质瘤细胞凋亡。SDF-1还介导胶质瘤趋化作用，这与趋化因子这一更为人熟知的作用相符。我们得出结论，胶质瘤细胞表达一种主要的趋化因子受体CXCR4，并且其部分功能是通过激活Akt等途径来调节存活。
