PDGF-D/PDGF-ββ Receptor-Regulated Chemotaxis of Malignant Mesothelioma Cells
PDGF-D/PDGF-ββ Receptor-Regulated Chemotaxis of Malignant Mesothelioma Cells
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DOI：
10.1159/000337605
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发表时间：
2012-01-01
影响因子：
--
通讯作者：
Nishizaki, Tomoyuki
中科院分区：
文献类型：
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作者：
Okada, Asuka;Yaguchi, Takahiro;Nishizaki, Tomoyuki
背景/目标：我们早期的研究表明，血小板衍生生长因子（PDGF）-β β受体调节人类恶性间皮瘤细胞，如MSTO-211 H，NCIH-2052，NCIH-2452和NCIH-28细胞的趋化性，但不调节非恶性Met 5A细胞。本研究旨在进一步了解趋化性背后的PDGF-β β受体信号。研究方法：对有和没有敲低PDGF-β β受体的细胞监测从细胞分泌的PDGF-D、Akt和ERK的活化以及细胞迁移。结果：FBS能显著促进恶性间皮瘤细胞PDGF-D的分泌，但对Met 5A细胞无明显影响。PDGF-D在肿瘤细胞和非肿瘤细胞中均可激活Akt和ERK。PDGF-D显著促进恶性间皮瘤细胞的迁移，但不是Met 5A细胞，其程度在细胞类型之间变化。PDGF-D的易化作用可通过敲低PDGF-beta β受体或PI 3激酶、PDK 1、Akt、Rac 1、ROCK和MEK的抑制剂来明显阻止。结论：本研究的结果表明，PDGF-D促进恶性间皮瘤细胞的趋化性，通过PDGF-beta β受体信号通路沿着PI 3激酶/PDK 1/Akt/Rac 1/ROCK轴和相关的ERK激活。版权所有（C）2012 S. Karger AG，巴塞尔
Background/Aims: Our earlier study suggested that platelet-derived growth factor (PDGF)-beta beta receptor regulates chemotaxis of human malignant mesothelioma cells such as MSTO-211H, NCIH-2052, NCIH-2452, and NCIH-28 cells, but not non-malignant Met5A cells. The present study was designed to gain further insight into the PDGF-beta beta receptor signals underlying the chemotaxis. Methods: PDGF-D secreted from cells, activation of Akt and ERK, and cell migration were monitored for cells with and without knocking-down PDGF-beta beta receptor. Results: FBS significantly stimulated PDGF-D secretion from malignant mesothelioma cells, but not Met5A cells. PDGF-D activated Akt and ERK in both the nonmalignant and malignant cells. PDGF-D significantly facilitated migration of malignant mesothelioma cells, but not Met5A cells, with the extent varying among the cell types. The facilitatory action of PDGF-D was clearly prevented by knocking-down PDGF-beta beta receptor or inhibitors of PI3 kinase, PDK1, Akt, Rac1, ROCK, and MEK. Conclusion: The results of the present study indicate that PDGF-D promotes malignant mesothelioma cell chemotaxis through PDGF-beta beta receptor signaling pathways along a PI3 kinase/PDK1/Akt/Rac1/ROCK axis and relevant to ERK activation. Copyright (C) 2012 S. Karger AG, Basel