Kim Chul-Ho, Kim Janghee, Kahng Hison, Choi Eun Chang
Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea.
Ann Surg Oncol. 2007 May;14(5):1565-74. doi: 10.1245/s10434-006-9320-5. Epub 2007 Feb 10.
Hepatocyte growth factor (HGF) is known to induce scattering in various epithelial cells, and E-cadherin plays important roles in the maintenance of cell-cell adhesion. However, the mechanisms surrounding these actions are not fully understood. Therefore, we examined how HGF affects the expression and distribution of E-cadherin. In addition, we observed the relationship between prognosis and modulation of E-cadherin by HGF in hypopharyngeal carcinoma.
Tumor tissues from 66 patients with hypopharyngeal squamous cell carcinoma were evaluated for the expression of HGF, its receptor (c-Met), and E-cadherin. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot test were performed on hypopharyngeal cancer tissues. The association and changes of E-cadherin with HGF treatment in a hypopharyngeal cancer cell line were investigated by RT-PCR, Western blot analysis, inhibition assay, immunofluorescence staining, and invasion assay.
E-cadherin expression was found in 87.9% of squamous cell carcinomas; these could be further classified as membranous type (46.9%) or nonmembranous type (53.1%). The expression of HGF in tumors with nonmembranous type E-cadherin expression was far higher than in tumors with membranous expression. Nonmembranous type E-cadherin expression correlated significantly with lymph node metastasis, distant metastasis, and recurrence (P < .05). HGF decreased the expression of E-cadherin and induced the translocation of E-cadherin to the cytoplasm. HGF and E-cadherin neutralizing antibody stimulated dispersion, and HGF significantly enhanced the invasion of hypopharyngeal cancer cells in a dose-dependent manner (P < .05).
These results suggest that HGF can modulate the expression and intracellular localization of E-cadherin in hypopharyngeal cancer cells. In addition, these results indicate that changes in E-cadherin by HGF can affect the prognosis of hypopharyngeal carcinoma.
已知肝细胞生长因子（HGF）可诱导多种上皮细胞发生散射，而E-钙黏蛋白在维持细胞间黏附中发挥重要作用。然而，围绕这些作用的机制尚未完全明确。因此，我们研究了HGF如何影响E-钙黏蛋白的表达和分布。此外，我们观察了下咽癌中HGF对E-钙黏蛋白的调节与预后之间的关系。
对66例下咽鳞状细胞癌患者的肿瘤组织进行HGF、其受体（c-Met）和E-钙黏蛋白表达的评估。在下咽癌组织上进行逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹试验。通过RT-PCR、蛋白质免疫印迹分析、抑制试验、免疫荧光染色和侵袭试验，研究下咽癌细胞系中E-钙黏蛋白与HGF处理的相关性及变化。
在87.9%的鳞状细胞癌中发现有E-钙黏蛋白表达；这些可进一步分为膜型（46.9%）或非膜型（53.1%）。非膜型E-钙黏蛋白表达的肿瘤中HGF的表达远高于膜型表达的肿瘤。非膜型E-钙黏蛋白表达与淋巴结转移、远处转移和复发显著相关（P < 0.05）。HGF降低了E-钙黏蛋白的表达，并诱导E-钙黏蛋白向细胞质转位。HGF和E-钙黏蛋白中和抗体刺激细胞分散，且HGF以剂量依赖性方式显著增强下咽癌细胞的侵袭能力（P < 0.05）。
这些结果表明，HGF可调节下咽癌细胞中E-钙黏蛋白的表达和细胞内定位。此外，这些结果表明HGF引起的E-钙黏蛋白变化可影响下咽癌的预后。
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