Signal processing in migrating T24 human bladder carcinoma cells: Role of the autocrine interleukin-8 loop
Signal processing in migrating T24 human bladder carcinoma cells: Role of the autocrine interleukin-8 loop
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DOI：
10.1002/ijc.10424
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发表时间：
2002-06-10
影响因子：
6.4
通讯作者：
Entschladen, F
中科院分区：
文献类型：
--
作者：
Lang, K;Niggemann, B;Entschladen, F
T24 人膀胱癌细胞在 3 维胶原基质内显示出高运动活性（70% 运动细胞）。这种高迁移活性是由白细胞介素 8 受体 A 的自分泌作用诱导的，如中和分泌的白细胞介素 8 的抗体所示。用这些特异性抗体处理细胞使运动活性降低一半。使用特定酶抑制剂证明，白细胞介素 8 诱导的 T24 运动的细胞内信号转导涉及蛋白酪氨酸激酶 (PTK)、磷脂酶 Cgamma (PLCgamma) 和蛋白激酶 C (PKC) 的活性。这些结果表明白细胞介素 8 诱导的人 T24 膀胱癌细胞迁移的调节信号转导模型如下：白细胞介素 8 受体（蛇纹石家族的一种受体）的参与导致了 β-抑制蛋白介导的 PTK 激活。这些激酶磷酸化 PLCgamma，产生第二信使二酰甘油 (DAG) 和肌醇 1,4,5-三磷酸 (IP3)。 DAG 激活 PKC，而 IP3 介导内质网钙的释放。通过共聚焦激光显微镜，我们观察到装载有钙染料 Fluo-3/AM 的迁移 T24 细胞中胞质钙浓度的振荡。在这里，我们报告了分泌型白介素 8 的新自分泌功能和细胞内信号转导，导致胞质钙的调节和迁移性肿瘤细胞表型。 (C) 2002 Wiley-Liss, Inc.
T24 human bladder carcinoma cells reveal a high locomotor activity (70% locomoting cells) within a 3-dimensional collagen matrix. This high migratory activity is induced by an autocrine engagement of the interleukin-8 receptor A, as was shown by antibodies neutralizing the secreted interleukin-8. Treatment of the cells with these specific antibodies reduced the locomotor activity by half. The intracellular signal transduction underlying the interleukin-8-induced T24 locomotion involves the activity of protein tyrosine kinases (PTKs), the phospholipase Cgamma (PLCgamma) and the protein kinase C (PKC), as proven by the use of specific enzyme inhibitors. These results suggest the following model for the regulatory signal transduction of interleukin-8-induced human T24 bladder carcinoma cell migration: The engagement of the interleukin-8-receptor, a receptor of the serpentine family, leads to the beta-arrestin-mediated activation of PTKs. These kinases phosphorylate the PLCgamma, which generates the second messengers diacylglycerol (DAG) and inositol-1,4,5-trisphosphate (IP3). DAG activates the PKC, whereas IP3 mediates the release of calcium from the endoplasmatic reticulum. By means of confocal laser microscopy, we observed an oscillation of the cytosolic calcium concentration in migrating T24 cells, which were loaded with the calcium-dye fluo-3/AM. Here, we report on a new autocrine function of secreted interleukin-8 and the intracellular signal transduction leading to the regulation of cytosolic calcium and to a migratory tumor cell phenotype. (C) 2002 Wiley-Liss, Inc.