Kitajima Daisuke, Kasamatsu Atsushi, Nakashima Dai, Miyamoto Isao, Kimura Yasushi, Endo-Sakamoto Yosuke, Shiiba Masashi, Tanzawa Hideki, Uzawa Katsuhiro
Department of Oral Science, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan.
Department of Dentistry and Oral-Maxillofacial Surgery, Graduate School of Medicine, Chiba University Hospital, Chuo-ku, Chiba 260-8670, Japan.
Oncol Lett. 2018 May;15(5):7237-7242. doi: 10.3892/ol.2018.8212. Epub 2018 Mar 8.
Angiopoietin-1 (Ang1) is a binding partner of endothelial cell-specific tyrosine-protein kinase receptor (Tie2), which serves important roles in vascular development and angiogenesis. Tie2 is closely associated with the metastasis of oral squamous cell carcinomas (OSCCs) however, little is known about the correlation between Tie2 and Ang1. In the present study, the functional mechanisms of the Tie2/Ang1 interaction were investigated using Tie2 overexpressed (oeTie2) OSCC cells and recombinant Ang1 protein. oeTie2 cells had increased cell-cell and cell-extracellular matrix adhesions compared with the control cells. Additionally, the adhesive activities increased following treatment with exogenous Ang1, indicating that Ang1 directly enhances Tie2 functions. In the clinical OSCC data from 10 cases positive for regional lymph node metastasis, all cases were negative for Tie2 expression and eight cases (80%) were negative for Ang1 expression. These results suggest that Tie2 and Ang1 serve important roles in cancer metastasis and may be potential biomarkers and therapeutic targets for OSCC metastasis.
血管生成素-1（Ang1）是内皮细胞特异性酪氨酸蛋白激酶受体（Tie2）的结合伴侣，在血管发育和血管生成中发挥重要作用。Tie2与口腔鳞状细胞癌（OSCC）的转移密切相关，然而，关于Tie2与Ang1之间的相关性知之甚少。在本研究中，使用过表达Tie2（oeTie2）的OSCC细胞和重组Ang1蛋白研究了Tie2/Ang1相互作用的功能机制。与对照细胞相比，oeTie2细胞的细胞间和细胞与细胞外基质的粘附增加。此外，用外源性Ang1处理后，粘附活性增加，表明Ang1直接增强Tie2功能。在10例区域淋巴结转移阳性的临床OSCC数据中，所有病例的Tie2表达均为阴性，8例（80%）的Ang1表达为阴性。这些结果表明，Tie2和Ang1在癌症转移中发挥重要作用，可能是OSCC转移的潜在生物标志物和治疗靶点。
