Lin Chiang-Liang, Chiang Wei-Fan, Tung Chao-Ling, Hsieh Jeng-Long, Hsiao Jenn-Ren, Huang Wen-Tsung, Feng Li-Yia, Chang Chi-Hua, Liu Shyun-Yeu, Tsao Chao-Jung, Feng Yin-Hsun
Department of Hematology and Oncology, Chi-Mei Medical Center, Liouying, Tainan 73657, Taiwan, R.O.C.
Department of Dentology, Chi-Mei Medical Center, Liouying, Tainan 73657, Taiwan, R.O.C.
Mol Med Rep. 2015 Jan;11(1):547-54. doi: 10.3892/mmr.2014.2700. Epub 2014 Oct 20.
Sprouty2 is known for its tumor-suppressing effect in various human malignant diseases. In head and neck squamous cell carcinoma (HNSCC), the role of sprouty2 in tumorigenesis and clinical implication remains elusive. The aim of the present study was to investigate the expression of sprouty2 in patients with HNSCC and its function in vitro. Quantitative analysis of mRNA expression of sprouty2 was performed on frozen tumor samples from 42 patients with HNSCC and 19 with oral verrucous hyperplasia (OVH) with paired counterparts of normal mucosa. Downregulation of sprouty2 expression was demonstrated in 79% of HNSCC samples and in 58% of OVH samples compared with paired samples of normal mucosa. Enhanced expression of sprouty2 protein suppressed the growth of HNSCC cells and signaling of the phosphorylated AKT pathway. Following transfection of the sprouty2 plasmid, HNSCC cells were more sensitive to sorafenib, a tyrosine kinase inhibitor of Raf and vascular endothelial growth factor receptor. The present study suggested that sprouty2 expression was downregulated and behaved as a tumor suppressor in HNSCC. Sprouty2 expression in tumor cells enhanced sensitivity to sorafenib. Further studies are required to define the clinical impact of sprouty2 in patients with HNSCC.
Sprouty2以其在多种人类恶性疾病中的肿瘤抑制作用而闻名。在头颈部鳞状细胞癌（HNSCC）中，Sprouty2在肿瘤发生中的作用及临床意义仍不明确。本研究的目的是调查HNSCC患者中Sprouty2的表达及其体外功能。对42例HNSCC患者和19例口腔疣状增生（OVH）患者的冷冻肿瘤样本及其配对的正常黏膜样本进行了Sprouty2 mRNA表达的定量分析。与配对的正常黏膜样本相比，79%的HNSCC样本和58%的OVH样本中Sprouty2表达下调。Sprouty2蛋白表达增强抑制了HNSCC细胞的生长以及磷酸化AKT途径的信号传导。转染Sprouty2质粒后，HNSCC细胞对索拉非尼（一种Raf和血管内皮生长因子受体的酪氨酸激酶抑制剂）更敏感。本研究表明，Sprouty2表达下调，在HNSCC中起肿瘤抑制作用。肿瘤细胞中Sprouty2表达增强了对索拉非尼的敏感性。需要进一步研究来确定Sprouty2对HNSCC患者的临床影响。
