Plasma Osteopontin, Hypoxia, and Response to Radiotherapy in Nasopharyngeal Cancer
Plasma Osteopontin, Hypoxia, and Response to Radiotherapy in Nasopharyngeal Cancer
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DOI：
10.1158/1078-0432.ccr-08-0364
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发表时间：
2008-11-01
影响因子：
11.5
通讯作者：
Chan, Anthony T. C.
中科院分区：
文献类型：
--
作者：
Hui, Edwin P.;Sung, Fion L.;Chan, Anthony T. C.
目的：近年来的研究表明，头颈癌细胞系中的骨桥蛋白是由缺氧诱导的，其血浆水平可作为肿瘤缺氧和头颈癌治疗结果的替代标志物。我们研究了骨桥蛋白对鼻咽癌细胞系体外缺氧的反应，并测定了鼻咽癌患者、非鼻咽癌头颈癌患者和健康对照者血浆骨桥蛋白水平。实验设计：鼻咽癌细胞株HK 1、HONE-1、C666-1和CNE-2分别在缺氧或常氧、+/-复氧条件下处理0 ~ 48 h，观察其对放疗反应的影响。通过ELISA测定来测量上清液中的骨桥蛋白分泌。Western blotting检测骨桥蛋白表达，RT-PCR检测骨桥蛋白mRNA表达。采用酶联免疫吸附法（ELISA）检测鼻咽癌患者（n = 66，其中鼻咽癌44例，头颈部癌22例）和正常对照组（n = 29）血浆骨桥蛋白水平。只有CNE-2分泌骨桥蛋白，缺氧对骨桥蛋白的分泌无明显诱导作用。转移性鼻咽癌和头颈癌患者血浆骨桥蛋白水平显著高于对照组，而局部鼻咽癌患者血浆骨桥蛋白水平无显著差异。在接受根治性放射治疗的局部鼻咽癌患者中（n = 31），高（>中位数）的治疗前血浆骨桥蛋白水平是放射治疗反应不良的重要预测因子（完全缓解率，40%对88%; P = 0.009），这在多变量分析中仍然是显著的。本研究结果提示，鼻咽癌放疗前血浆骨桥蛋白水平可能是鼻咽癌放疗反应的一个有用的生物标志物。
Purpose: Recent studies have suggested that osteopontin is induced by hypoxia in head and neck cancer cell lines and its plasma level may serve as a surrogate marker for tumor hypoxia and treatment outcome in head and neck cancer. We investigated the response of osteopontin to in vitro hypoxia in nasopharyngeal carcinoma cell lines, and determined plasma osteopontin levels in nasopharyngeal carcinoma patients, nonnasopharyngeal carcinoma head and neck cancer patients, and healthy controls. We explored the relationship of plasma osteopontin and response to radiotherapy in nasopharyngeal carcinoma.Experimental Design: Nasopharyngeal carcinoma cell lines HK1, HONE-1, C666-1, and CNE-2 were treated with 0 to 48 hours of hypoxia or normoxia, +/- reoxygenation. Osteopontin secretion in the supernatant was measured by ELISA assay. Cellular osteopontin protein and m RNA were detected by Western blotting and reverse transcription-PCR, respectively. Plasma osteopontin levels in patients (n = 66; 44 nasopharyngeal carcinoma, 22 head and neck cancer) and controls (n = 29) were measured by ELISA.Results: Hypoxia has no effect on osteopontin protein and mRNA level in nasopharyngeal carcinoma cells. Only CNE-2 secreted osteopontin, and there was no significant induction by hypoxia. Plasma osteopontin levels in patients of metastatic nasopharyngeal carcinoma and head and neck cancer, but not in locoregional nasopharyngeal carcinoma, were significantly higher than in controls. In patients with locoregional nasopharyngeal carcinoma receiving curative radiotherapy (n = 31), a high (>median) pretreatment plasma osteopontin level was a significant predictor of poor response to radiotherapy (complete response rate, 40% versus 88%; P = 0.009), which remained significant in multivariate analysis.Conclusion: Our results suggested that the pretreatment plasma osteopontin level may be a useful biomarker of response to radiotherapy in nasopharyngeal carcinoma.