Department of Oral and Cranio-Maxillofacial Surgery, University of Luebeck, Germany.
Radiother Oncol. 2011 Oct;101(1):93-9. doi: 10.1016/j.radonc.2011.07.032. Epub 2011 Aug 30.
Radiation-induced xerostomia still represents a common symptom following radiotherapy of head and neck malignancies, which significantly impairs the patient's quality of life. In this cross-sectional study, human salivary glands were investigated to assess the role of Wnt/β-catenin and TGF-β pathways in the pathogenic process of radiogenic impairment of salivary function.
Irradiated human salivary glands were investigated in patients with manifested xerostomia. Alteration of Wnt-1 and cell-cell adhesion was evaluated immunohistologically as well as changes in the expression of TGF-β were assessed in salivary gland tissue.
We assessed two alteration patterns in which Wnt-1 expression represents one change along with up-regulation of β-catenin and E-cadherin in irradiated but viable acinar cells. Increased expression of tenascin-C was observed in sites of epithelial-mesenchymal interaction and loss of cell-cell adhesion was assessed in translocated epithelial cells in the stroma.
Increased transdifferentiation and remodeling of acinar structures was associated with decrease of viable acinar structures. The role of Wnt and TGF signaling may provide a potential therapeutic approach to prevent radiation-induced damage to salivary glands during radiotherapy for head and neck cancer.
放射性口干症仍然是头颈部恶性肿瘤放疗后的常见症状,严重影响患者的生活质量。在这项横断面研究中,我们研究了人唾液腺,以评估 Wnt/β-catenin 和 TGF-β 通路在放射性唾液功能障碍发病机制中的作用。
研究了表现出口干症的患者的放射性唾液腺。免疫组织化学评估 Wnt-1 和细胞间黏附的改变,以及唾液腺组织中 TGF-β 的表达变化。
我们评估了两种改变模式,其中 Wnt-1 表达代表一种变化,同时伴有放射性存活的腺泡细胞中 β-catenin 和 E-钙黏蛋白的上调。在上皮-间充质相互作用部位观察到腱蛋白-C 的表达增加,并且在基质中的转位上皮细胞中评估到细胞间黏附的丧失。
增加的腺泡结构的转分化和重塑与存活的腺泡结构的减少有关。Wnt 和 TGF 信号的作用可能为预防头颈部癌症放疗期间唾液腺的放射性损伤提供一种潜在的治疗方法。