Modulation of Sodium/Iodide Symporter Expression in the Salivary Gland
Modulation of Sodium/Iodide Symporter Expression in the Salivary Gland
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DOI：
10.1089/thy.2012.0571
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发表时间：
2013-08-01
期刊：
影响因子：
6.6
通讯作者：
Jhiang, Sissy M.
中科院分区：
文献类型：
--
作者：
La Perle, Krista M. D.;Kim, Dong Chul;Jhiang, Sissy M.
背景资料：碘-131治疗甲状腺癌后，唾液腺中钠/碘同向转运体（NIS）介导的生理性碘摄取使其对放射性碘诱导的损伤易感。由于复发性涎腺炎和持续性口干，甲状腺癌幸存者的后续生活质量可能会下降。NIS在三个主要的涎腺导管组件在各种病理条件下的表达进行了检查，以更好地了解NIS调制在salivarygland.Methods：NIS表达进行了评价，免疫组化在人类唾液腺组织微阵列构建的正常，发炎，和肿瘤唾液组织核心。在50名甲状腺癌患者中，在给予I-123后24小时，通过单光子发射计算机断层扫描/计算机断层扫描成像评价了反映NIS活性与下颌下和腮腺唾液分泌物清除率组合的累积I-123放射性。NIS在大多数纹管的基底外侧膜中高度表达，但在少数闰管和排泄管细胞中弱表达。腮腺和下颌下腺之间的I-123蓄积比为2.38 +/-0.19。然而，通过目标体积归一化的I-123蓄积的相应比率为1.19 +/-0.06。颌下唾液腺中NIS阳性的纹状管细胞的百分比在统计学上大于腮腺唾液腺，表明颌下唾液腺中唾液分泌物的清除率更高。NIS在涎腺炎的纹状管中的表达不均匀地减少或缺失。大部分导管型涎腺肿瘤不表达NIS。然而，Warthin的肿瘤的纹状管起源表现出一致的和强烈的NIS染色，对应于放射性碘intake. Conclusions：NIS表达紧密调制的过渡过程中的闰管和横纹分泌管的唾液导管细胞。NIS在唾液腺中的表达在炎症和肿瘤形成期间减少。进一步的研究可能会确定在放射性碘治疗期间允许选择性抑制唾液腺中NIS表达/活性的分子靶点和/或药理学试剂。
Background: Physiologic iodide-uptake, mediated by the sodium/iodide symporter (NIS), in the salivary gland confers its susceptibility to radioactive iodine-induced damage following I-131 treatment of thyroid cancer. Subsequent quality of life for thyroid cancer survivors can be decreased due to recurrent sialoadenitis and persistent xerostomia. NIS expression at the three principal salivary duct components in various pathological conditions was examined to better our understanding of NIS modulation in the salivary gland.Methods: NIS expression was evaluated by immunohistochemistry in human salivary gland tissue microarrays constructed of normal, inflamed, and neoplastic salivary tissue cores. Cumulative I-123 radioactivity reflecting the combination of NIS activity with clearance of saliva secretion in submandibular and parotid salivary glands was evaluated by single-photon emission computed tomography/computed tomography imaging 24 hours after I-123 administration in 50 thyroid cancer patients.Results: NIS is highly expressed in the basolateral membranes of the majority of striated ducts, yet weakly expressed in few intercalated and excretory duct cells. The ratio of I-123 accumulation between parotid and submandibular glands is 2.38 +/- 0.19. However, the corresponding ratio of I-123 accumulation normalized by volume of interest is 1.19 +/- 0.06. The percentage of NIS-positive striated duct cells in submandibular salivary glands was statistically greater than in parotid salivary glands, suggesting a higher clearance rate of saliva secretion in submandibular salivary glands. NIS expression in striated ducts was heterogeneously decreased or absent in sialoadenitis. Most ductal salivary gland tumors did not express NIS. However, Warthin's tumors of striated duct origin exhibited consistent and intense NIS staining, corresponding with radioactive iodine uptake.Conclusions: NIS expression is tightly modulated during the transition of intercalated to striated ducts and striated to excretory ducts in salivary ductal cells. NIS expression in salivary glands is decreased during inflammation and tumor formation. Further investigation may identify molecular targets and/or pharmacologic agents that allow selective inhibition of NIS expression/activity in salivary glands during radioactive iodine treatment.