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首页> 外文期刊>Journal of Cellular Physiology >LRRC4 inhibits glioblastoma cell proliferation, migration, and angiogenesis by downregulating pleiotropic cytokine expression and responses.
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LRRC4 inhibits glioblastoma cell proliferation, migration, and angiogenesis by downregulating pleiotropic cytokine expression and responses.

机译:LRRC4抑制胶质母细胞瘤细胞增殖,通过下调迁移和血管生成多效性的细胞因子表达和响应。

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Leucine-rich repeat C4 (LRRC4) has been shown to inhibit glioma cell proliferation, however, little is known about the mechanism(s) underlying the action of LRRC4. Here, we show that two glioblstoma U251 cell clones stably expressing LRRC4 were established. LRRC4 expression significantly inhibited the expression of some cytokines and their receptors determined by microarray and Western blot assays, and dramatically reduced cytokine-induced AP-1, NF-kB, and CyclinD1 activation in glioma cells. Furthermore, LRRC4 expression in glioma cells significantly downregulated spontaneous and cytokine-induced expression of K-RAS and phosphorylation of c-Raf, ERK, AKT, NF-kBp65, p70S6K, and PKC, suggesting that LRRC4 inhibited receptor tyrosine kinase (RTK) signaling pathways. Moreover, treatment with bFGF, IGF1, or IGF2 stimulated LRRC4(-/-), but not the LRRC4(+), glioma cell proliferation, indicating that LRRC4 mitigated cytokine-stimulated proliferation in glioma cells. In addition, treatment of LRRC4(-/-) glioma cells with EGF, IGF2, or PDGF promoted long distance mobilization, but induced little migration in LRRC4(+) glioma cells, suggesting that LRRC4 retarded cytokine-promoted glioma cell migration in vitro. Finally, human vessel endothelial cells (ECV304) treated with VEGF grew, aligned and formed hollow tube-like structures in vitro. In contrast, LRRC4(+) ECV304 treated with VEGF failed to form vessel-tube structures. Collectively, LRRC4 expression inhibited the expression of some growth factors, cytokines and their receptors, and the capacity of glioma cells responding to cytokine stimulation, leading to inhibition of glioma cell proliferation. Conceivably, induction of LRRC4 expression may provide new intervention for human glioma in the clinic.
机译:富亮氨酸重复C4 (LRRC4)已被证明然而,抑制神经胶质瘤细胞增殖人们很少知道(s)底层机制LRRC4的作用。glioblstoma U251细胞克隆稳定表达建立了LRRC4。显著抑制一些的表达细胞因子及其受体所决定微阵列和免疫印迹分析,细胞因子诱导的AP-1显著下降,在神经胶质瘤细胞NF-kB, CyclinD1激活。此外,LRRC4表达在神经胶质瘤细胞显著下调自发的和细胞因子诱导的k - ras基因的表达NF-kBp65 ERK的磷酸化c-Raf,一种蛋白激酶,p70S6K PKC,表明LRRC4抑制受体酪氨酸激酶(RTK)信号通路。IGF2刺激LRRC4(- / -),但不是LRRC4 (+),神经胶质瘤细胞增殖,表明LRRC4减轻cytokine-stimulated扩散在神经胶质瘤细胞。LRRC4(- / -)神经胶质瘤细胞EGF, IGF2和PDGF促进了长途动员,但诱导小迁移LRRC4(+)神经胶质瘤细胞,这表明LRRC4弱智cytokine-promoted神经胶质瘤细胞体外迁移。血管内皮细胞(ECV304)处理VEGF增加,对齐,形成中空的管状结构体外。vessel-tube VEGF未能处理形式结构。抑制一些生长因子的表达,细胞因子及其受体,和能力神经胶质瘤细胞对细胞因子刺激,导致神经胶质瘤细胞的抑制作用扩散。表达可能为人类提供新的干预神经胶质瘤的诊所。

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