Department of Oromaxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Heping District, Shenyang, Liaoning 110002, PR China.
Int J Mol Med. 2011 May;27(5):679-87. doi: 10.3892/ijmm.2011.628. Epub 2011 Feb 23.
The mechanisms leading to squamous cell carcinoma of the head and neck (SCCHN) metastasis are incompletely understood. Although evidence shows that the chemokine receptor 7 (CCR7) and its ligand CCL19 may regulate tumor dissemination, their role in SCCHN is not clearly defined. CCR7 has been shown to regulate integrins, which facilitate adhesion of cancer cells to and/or migration through the extracellular matrix (ECM). To investigate the relationship between CCR7 and integrin αvβ3 in metastatic SCCHN, we used adhesion and migration assays, immunofluorescence staining and western blotting to determine whether integrin αvβ3 can be activated by CCL19 in the metastatic SCCHN cell line PCI-37B, which was pre-incubated with CCL19 or the integrin αvβ3 inhibitor, IS201. Our results demonstrate that CCR7 favors PCI-37B cell adhesion and migration, induces reorganization of the actin cytoskeleton and induces integrin αvβ3 phosphorylation. The integrin αvβ3 inhibitor, IS201, blocked all of these effects. CCR7 and integrin αvβ3 expression significantly and positively correlated with tumor size, clinical stage and nodal metastasis. Taken together, our data indicate that CCR7 regulates cell adhesion and migration via integrin αvβ3 in metastatic SCCHN. These results should provide the groundwork for new strategies aimed at preventing SCCHN metastasis.
导致头颈部鳞状细胞癌 (SCCHN) 转移的机制尚不完全清楚。尽管有证据表明趋化因子受体 7 (CCR7) 及其配体 CCL19 可能调节肿瘤扩散，但它们在 SCCHN 中的作用尚不清楚。已经表明 CCR7 调节整合素，整合素促进癌细胞与细胞外基质 (ECM) 的黏附和/或迁移。为了研究 CCR7 与转移性 SCCHN 中整合素 αvβ3 之间的关系，我们使用黏附和迁移测定、免疫荧光染色和 Western blot 来确定整合素 αvβ3 是否可以被 CCL19 激活在预先用 CCL19 或整合素 αvβ3 抑制剂 IS201 孵育的转移性 SCCHN 细胞系 PCI-37B 中。我们的结果表明，CCR7 有利于 PCI-37B 细胞的黏附和迁移，诱导肌动蛋白细胞骨架的重排，并诱导整合素 αvβ3 磷酸化。整合素 αvβ3 抑制剂 IS201 阻断了所有这些作用。CCR7 和整合素 αvβ3 的表达与肿瘤大小、临床分期和淋巴结转移显著正相关。综上所述，我们的数据表明 CCR7 通过整合素 αvβ3 调节转移性 SCCHN 中的细胞黏附和迁移。这些结果应为旨在预防 SCCHN 转移的新策略提供基础。
