Role of interleukin-8 secreted from human oral squamous cell carcinoma cell lines.
Role of interleukin-8 secreted from human oral squamous cell carcinoma cell lines.
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DOI：
10.1016/s1368-8375(02)00006-4
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发表时间：
2002-10
期刊：
影响因子：
4.8
通讯作者：
Hitoshi Watanabe;M. Iwase;M. Ohashi;M. Nagumo
中科院分区：
文献类型：
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作者：
Hitoshi Watanabe;M. Iwase;M. Ohashi;M. Nagumo
白细胞介素-8 （IL-8）是多种恶性肿瘤中参与肿瘤生长和血管生成的重要细胞因子。此外，基质金属蛋白酶（matrix metalloptoteinases, MMPs）在口腔鳞状细胞癌（oral squamous cell carcinoma， OSCC）等肿瘤的侵袭和转移过程中也发挥着重要作用。我们研究IL-8和MMPs是否参与OSCC的发生和转移。首先，我们研究了IL-8和IL-8受体（IL-8R）的基因和蛋白表达，以及IL-8对OSCC增殖、迁移和侵袭的影响。其次，我们也因此研究了IL-8对OSCC细胞中MMP释放的影响。骨鳞癌细胞株NA和HSC-4在体外组成性表达IL-8 mRNA并分泌IL-8蛋白。添加肿瘤坏死因子(TNF)-α和IL-β可显著提高IL-8的产生，但不影响干扰素(IFN)-γ、粒细胞-巨噬细胞集落刺激因子（GM-CSF）或IL-2的产生。流式细胞术分析显示，IL-8、IL-8RA和IL-8RB两种受体在OSCC细胞系中均有组成性表达。IL-8受体在HSC-4细胞中的表达强于NA细胞。各细胞系IL-8RA表达强度均强于IL-8RB表达强度。IL-8受体的表达不受TNF-α和IL-1β等细胞因子的影响。含有OSCC细胞株IL-8的条件培养基诱导了OSCC细胞的迁移和侵袭，但不改变细胞的增殖。NA细胞和HSC-4细胞的迁移和侵袭能力差异与各细胞系中IL-8受体的表达强度有关。IL-8、IL-8RA和IL-8RB的中和抗体部分抑制条件培养基诱导的趋化活性。在这些OSCC细胞株的培养上清液中检测到MMP-2、-7和-9的表达。il -8的加入增强了MMP-7蛋白和mRNA的表达，但其他MMPs的表达无明显差异。这些结果提示，从OSCC分泌的IL-8可能通过调控MMP-7的表达参与OSCC的侵袭。
Interleukin-8 (IL-8) is an important cytokine involved in tumor growth and angiogenesis in a variety of malignancies. Furthermore, matrix metalloptoteinases (MMPs) also play important roles in the invasion and metastasis of carcinomas including oral squamous cell carcinoma (OSCC). We studied whether IL-8 and MMPs participate in tumorigenesis and metastasis of OSCC. First, we investigated the gene and protein expressions of IL-8 and IL-8 receptor (IL-8R), and the effect of IL-8 on proliferation, migration and invasion of OSCC. Second, we thus also investigated the effect of IL-8 on MMP release in OSCC cells. OSCC cell lines NA and HSC-4 constitutively expressed IL-8 mRNA and secreted its protein in vitro. The production of IL-8 was significantly enhanced by the addition of tumor necrosis factor (TNF)-α and IL-β, but not interferon (IFN)-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF) or IL-2. Flow cytometric analysis revealed the constitutive expression of both receptors of IL-8, IL-8RA and IL-8RB, in OSCC cell lines. The expression of IL-8 receptors in HSC-4 cells was stronger than that in NA cells. The intensity of IL-8RA expression was stronger than that of IL-8RB expression in each cell line. The expression of IL-8 receptors was not altered by the addition of cytokines such as TNF-α and IL-1β. The conditioned medium containing IL-8 from OSCC cell lines induced migration and invasion of OSCC cells, but did not change cell proliferation. The differences in migrational and invasive ability between NA cells and HSC-4 cells were correlated with the expression intensity of IL-8 receptors in each cell line. Neutralizing antibodies to IL-8, IL-8RA and IL-8RB partially inhibited the chemotactic activity induced by conditioned medium. The expression of MMP-2, -7 and -9 was detected in culture supernatants from these OSCC cell lines. The expressions of MMP-7 protein and mRNA were enhanced by the addition of rIL-8, but that of other MMPs was not observed in a similar manner. These results suggest that IL-8 secreted from OSCC may contribute to the invasion of OSCC through the regulation of MMP-7 expression.