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首页> 外文期刊>Oncogene >FGF5 as an oncogenic factor in human glioblastoma multiforme: autocrine and paracrine activities
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FGF5 as an oncogenic factor in human glioblastoma multiforme: autocrine and paracrine activities

机译：FGF5作为人胶质母细胞瘤的致癌因子：自分泌和旁分泌活性

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Fibroblast growth factor 5 (FGF5) is widely expressed in embryonic but scarcely in adult tissues. Here we report simultaneous overexpression of FGF5 and its predominant high-affinity receptor (FGFR1 IIIc) in astrocytic brain tumour specimens (N=49) and cell cultures (N=49). The levels of both ligand and receptor increased with enhanced malignancy in vivo and in vitro. Furthermore, secreted FGF5 protein was generally present in the supernatants of glioblastoma (GBM) cells. siRNA-mediated FGF5 downmodulation reduced moderately but significantly GBM cell proliferation while recombinant FGF5 (rFGF5) increased this parameter preferentially in cell lines with low endogenous expression levels. Apoptosis induction by prolonged serum starvation was significantly prevented by rFGF5. Moreover, tumour cell migration was distinctly stimulated by rFGF5 but attenuated by FGF5 siRNA. Blockade of FGFR1-mediated signals by pharmacological FGFR inhibitors or a dominant-negative FGFR1 IIIc protein inhibited GBM cell proliferation and/or induced apoptotic cell death. Moreover, rFGF5 and supernatants of highly FGF5-positive GBM cell lines specifically stimulated proliferation, migration and tube formation of human umbilical vein endothelial cells. In summary, we demonstrate for the first time that FGF5 contributes to the malignant progression of human astrocytic brain tumours by both autocrine and paracrine effects.
机译：成纤维细胞生长因子5（FGF5）在胚胎中广泛表达，但在成人组织中很少表达。在这里，我们报道在星形细胞肿瘤标本（N = 49）和细胞培养物中（N = 49），FGF5及其主要的高亲和力受体（FGFR1 IIIc）同时过表达。随着体内和体外恶性肿瘤的增强，配体和受体的水平均增加。此外，分泌的FGF5蛋白通常存在于胶质母细胞瘤（GBM）细胞的上清液中。 siRNA介导的FGF5下调适度降低，但显着降低GBM细胞增殖，而重组FGF5（rFGF5）在低内源表达水平的细胞系中优先提高此参数。 rFGF5可以显着防止长时间血清饥饿引起的细胞凋亡。此外，rFGF5明显刺激肿瘤细胞迁移，但FGF5 siRNA抑制肿瘤细胞迁移。药理FGFR抑制剂或显性负性FGFR1 IIIc蛋白对FGFR1介导的信号的阻断可抑制GBM细胞增殖和/或诱导凋亡性细胞死亡。此外，rFGF5和高度FGF5阳性的GBM细胞系的上清液特异性刺激人脐静脉内皮细胞的增殖，迁移和管形成。总之，我们首次证明了FGF5通过自分泌和旁分泌作用促进人类星形细胞肿瘤的恶性进展。

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