Nagler Rafael, Ben-Izhak Ofer, Savulescu Dana, Krayzler Ella, Akrish Sharon, Leschiner Svetlana, Otradnov Irina, Zeno Sivan, Veenman Leo, Gavish Moshe
Department of Oral and Maxillofacial Surgery and Laboratory of Oral Biochemistry, Rambam Medical Center and the Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, 31096, Israel.
Biochim Biophys Acta. 2010 May;1802(5):454-61. doi: 10.1016/j.bbadis.2010.01.008. Epub 2010 Jan 18.
Oral cancer features high rates of mortality and morbidity, and is in dire need for new approaches. In the present study we analyzed 18 kDa translocator protein (TSPO) expression in oral (tongue) cancer tumors by immunohistochemistry. We also assayed TSPO binding in human tongue cancer cell lines and in the cellular fraction of saliva from tongue cancer patients, heavy cigarette smokers, and non-smoking healthy people as controls. Concurrently, TSPO protein levels, cell viability, mitochondrial membrane potential (Deltapsi(m)), and general protein levels were analyzed. TSPO expression could be significantly enhanced in oral cancer tumors, compared to unaffected adjacent tissue. We also found that five-year survival probability dropped from 65% in patients with TSPO negative tumors to 7% in patients with highly expressed TSPO (p<0.001). TSPO binding capacity was also pronounced in the human oral cancer cell lines SCC-25 and SCC-15 (3133+/-643 fmol/mg protein and 6956+/-549 fmol/mg protein, respectively). Binding decreased by 56% and 72%, in the SCC-25 and SCC-15 cell lines, respectively (p<0.05) following CS exposure in cell culture. In the cellular fraction of saliva of heavy smokers TSPO binding was lower than in non-smokers (by 53%, p<0.05). Also the cellular fraction of saliva exposed to CS in vitro showed decreased TSPO binding compared to unexposed saliva (by 30%, p<0.001). Interestingly, oral cancer patients also displayed significantly lower TSPO binding in the cellular fraction of saliva compared to healthy controls (by 40%, p<0.01). Our results suggest that low TSPO binding found in the cellular fraction of saliva may depend on genetic background as well as result from exposure to CS. We suggest that this may be related to a predisposition for occurrence of oral cancer.
口腔癌具有很高的死亡率和发病率，迫切需要新的治疗方法。在本研究中，我们通过免疫组织化学分析了口腔（舌）癌肿瘤中18 kDa转位蛋白（TSPO）的表达。我们还检测了人舌癌细胞系以及舌癌患者、重度吸烟者和作为对照的非吸烟健康人的唾液细胞组分中的TSPO结合情况。同时，分析了TSPO蛋白水平、细胞活力、线粒体膜电位（Δψm）和总蛋白水平。与未受影响的相邻组织相比，口腔癌肿瘤中的TSPO表达可显著增强。我们还发现，TSPO阴性肿瘤患者的五年生存率从65%降至TSPO高表达患者的7%（p<0.001）。TSPO结合能力在人口腔癌细胞系SCC-25和SCC-15中也很明显（分别为3133±643 fmol/mg蛋白和6956±549 fmol/mg蛋白）。在细胞培养中暴露于香烟烟雾（CS）后，SCC-25和SCC-15细胞系中的结合分别下降了56%和72%（p<0.05）。在重度吸烟者的唾液细胞组分中，TSPO结合低于非吸烟者（低53%，p<0.05）。此外，与未暴露的唾液相比，体外暴露于CS的唾液细胞组分显示TSPO结合减少（低30%，p<0.001）。有趣的是，与健康对照相比，口腔癌患者唾液细胞组分中的TSPO结合也显著降低（低40%，p<0.01）。我们的结果表明，在唾液细胞组分中发现的低TSPO结合可能取决于遗传背景以及接触CS的结果。我们认为这可能与口腔癌发生的易感性有关。
