Chemokine CCL2 facilitates ICAM-1-mediated interactions of cancer cells and lymphatic endothelial cells in sentinel lymph nodes
Chemokine CCL2 facilitates ICAM-1-mediated interactions of cancer cells and lymphatic endothelial cells in sentinel lymph nodes
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DOI：
10.1111/j.1349-7006.2008.01064.x
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发表时间：
2009-03-01
期刊：
影响因子：
5.7
通讯作者：
Ohhashi, Toshio
中科院分区：
文献类型：
--
作者：
Kawai, Yoshiko;Kaidoh, Maki;Ohhashi, Toshio
我们使用免疫组织化学染色或蛋白质印迹分析检查了 CCL1、CCL2、CCL12 和 CCL21 对培养的人淋巴内皮细胞中粘附分子表达的影响。此外，我们还研究了表达的粘附分子是否能够促进癌细胞粘附到淋巴管内皮细胞作为体外微转移模型。 CCL2 导致人淋巴内皮细胞选择性显着表达 ICAM-1，但 CCL1、CCL12 和 CCL21 则不然。通过将刺激时间从 4 小时增加到 18 小时和 48 小时，ICAM-1 的免疫反应强度以时间依赖性方式显着增加，直至 18 小时。 ICAM-1 mRNA 水平在 18 小时内也显着升高。 CCL2 介导的 ICAM-1 免疫组织化学表达呈剂量依赖性从 10 pg/mL 增加至 1 ng/mL。使用特异性 CCL2 抗体中和 CCL2，可显着降低 CCL2 介导的 ICAM-1 表达。 CCL2 处理 18 小时可显着促进 MDA-MB-231 和 MCF-7 细胞体外附着至淋巴管内皮细胞 (LEC)。通过中和 CCL2 或通过抗 ICAM-1 抗体的额外处理，附着测定中 CCL2 介导的反应也显着降低。在从乳腺癌患者分离的前哨淋巴结的转移区域周围和内部强烈观察到 ICAM-1（而非 E-选择素）的免疫组织化学表达。这些发现表明，CCL2在培养的人淋巴管内皮细胞上诱导ICAM-1的选择性和显着表达，然后促进癌细胞附着于淋巴管内皮细胞，从而通过ICAM-1的过表达提供体外微转移模型。 （《癌症科学》2009 年；100：419-428）。
We examined the effects of CCL1, CCL2, CCL12 and CCL21 on the expression of adhesion molecules in cultured human lymphatic endothelial cells using immunohistochemical staining or Western blot analysis. In addition, we investigated whether the expressed adhesion molecule was able to facilitate the attachment of carcinoma cells to the lymphatic endothelial cells as an in vitro micrometastatic model. CCL2 caused a selective and significant expression of ICAM-1 on human lymphatic endothelial cells but CCL1, CCL12 and CCL21 did not. By increasing the stimulation time from 4 to 18 and 48 h, the intensity of immunoreactivity for ICAM-1 was significantly increased in a time-dependent manner up to 18 h. The ICAM-1 mRNA levels were also elevated significantly up to 18 h. The CCL2-mediated immunohistochemical expression of ICAM-1 was dose-dependently increased from 10 pg/mL to 1 ng/mL. The CCL2-mediated expression of ICAM-1 was significantly reduced by neutralization of CCL2 using a specific CCL2 antibody. The 18-h treatment with CCL2 caused a significant facilitation of in vitro attachment of MDA-MB-231 and MCF-7 cells to the lymphatic endothelial cells (LECs). The CCL2-mediated response in the attachment assay was also significantly reduced either by the neutralization of CCL2 or by additional treatment with anti-ICAM-1 antibody. Immunohistochemical expression of ICAM-1, but not E-selectin, was strongly observed around and within the metastatic region of sentinel lymph node isolated from breast cancer patients. These findings suggest that CCL2 induces selective and significant expression of ICAM-1 on cultured human lymphatic endothelial cells and then facilitates the attachment of carcinoma cells to the lymphatic endothelial cells, thus providing an in vitro micrometastatic model via the overexpression of ICAM-1. (Cancer Sci 2009; 100: 419-428).