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Biological activity of head and neck cancer cell lines with regard to IL-6 and MMP

头颈癌细胞系 IL-6 和 MMP 的生物活性

基本信息

批准号：
12671679
负责人：
NISHINO Hiroshi
金额：
$ 2.05万
依托单位：
Jichi medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

项目摘要

We established NKO-1, a SCC cell line that produces high levels of G-CSF and IL-6, from a metastatic lymph node obtained from a patient with a poorly differentiated maxillary SCC. We studied the in vitro effect of G-CSF and IL-6 on the growth of NKO-1, the in vitro effect of neutralizing G-CSF on the growth of NKO-1 normally enhanced by rhG-CSF, and invasion assay. The in vitro growth of NKO-1 cells was enhanced by high concentrations of G-CSF, but not by any concentration of hIL-6. The effect of G-CSF on NKO-1 cell growth was reduced by antibody to G-CSF in a dose-dependent manner. Compared with other cell lines, which produce low levels of G-CSF and IL-6, NKO-1 cells showed strong invasiveness.Cancer cells of head and neck cancer cell lines have IL-6 receptors (RT-PCR). The levels of those IL-6 receptors were reduced by antibody to IL-6 receptors in a dose-dependent manner. The in vitro growth rates of cancer cells of head and neck cancer cells lines were reduced by IL-6. We studied the invasiveness of cancer cells of head and neck cancer cell lines with IL-6 in an extracellular matrix membrane system. The degree of invasiveness was enhanced by incubating cells with IL-6. In addition G-CSF enhanced the invasiveness of tumor cells that produced large amounts of G-CSF.Low efficiency of transgene expression can be a problem in some applications that require potent gene expression such as antitumor applications. We demonstrate that AAV vector harbouring the HSVtk is able to kill cancer cells more efficiently when used in combination with γ-ray irradiation. γ-rays enhance rAAV-mediated transegene expression.

我们建立了NKO-1，一个SCC细胞系，产生高水平的G-CSF和IL-6，从一个转移性淋巴结，从一个低分化的上颌SCC患者。本实验研究了G-CSF和IL-6对NKO-1细胞体外生长的影响，中和G-CSF对rhG-CSF促进的NKO-1细胞体外生长的影响，以及侵袭实验。NKO-1细胞的体外生长被高浓度的G-CSF增强，但不被任何浓度的hIL-6增强。抗G-CSF抗体以剂量依赖性方式降低G-CSF对NKO-1细胞生长的影响。与其他细胞系相比，NKO-1细胞具有较强的侵袭力，而G-CSF和IL-6的产生水平较低。这些IL-6受体的水平被IL-6受体抗体以剂量依赖性方式降低。头颈癌细胞系的癌细胞的体外生长速率被IL-6降低。我们研究了在细胞外基质膜系统中用IL-6对头颈癌细胞系的癌细胞的侵袭性。通过将细胞与IL-6孵育来增强侵袭性的程度。此外，G-CSF增强了产生大量G-CSF的肿瘤细胞的侵袭力。在一些需要有效基因表达的应用中，例如抗肿瘤应用，转基因表达的低效率可能是一个问题。我们证明了携带HSVtk的AAV载体在与γ射线照射组合使用时能够更有效地杀死癌细胞。γ射线增强rAAV介导的转基因表达。