Ma Si-Rui, Mao Liang, Deng Wei-Wei, Li Yi-Cun, Bu Lin-Lin, Yu Guang-Tao, Zhang Wen-Feng, Sun Zhi-Jun
The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education.
The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral BiomedicineMinistry of Education; Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan UniversityWuhan, China.
Am J Transl Res. 2017 Feb 15;9(2):507-519. eCollection 2017.
Salivary adenoid cystic carcinoma (AdCC) is a common head and neck cancer with the propensity for local spread and distant metastasis. In our previous study, elevated expression of Anterior gradient 2 (AGR2) was detected in head and neck squamous cell carcinoma (HNSCC), associated with epithelial-mesenchymal transition (EMT) and cancer stemness. However, to date, the expression and function of AGR2 in AdCC has yet to be elucidated. In the present study, human AdCC tissue microarrays including 18 cases of normal salivary gland (NSG), 12 cases of pleomorphic adenoma (PMA) and 72 cases of AdCC were employed for immunohistochemical staining analysis. Results indicated that AGR2, which was remarkably correlated with Ki-67, transforming growth factor beta-1 (TGF-β1) and CD147, was significantly elevated in human salivary AdCC tissues. Knockdown of AGR2 significantly repressed the proliferation and migration of human SACC-83 and SACC-LM cell lines. Additionally, AGR2 silencing obviously reversed the EMT phenomena induced by TGF-β1. Taken together, our present study revealed the potential pro-metastasis role of AGR2 in AdCC, indicating that AGR2 might be a novel therapeutic target of AdCC with distant metastasis.
涎腺腺样囊性癌（AdCC）是一种常见的头颈部癌症，具有局部扩散和远处转移的倾向。在我们之前的研究中，在前梯度2（AGR2）在头颈部鳞状细胞癌（HNSCC）中检测到表达升高，与上皮-间质转化（EMT）和癌症干性相关。然而，迄今为止，AGR2在AdCC中的表达和功能尚未阐明。在本研究中，使用包括18例正常涎腺（NSG）、12例多形性腺瘤（PMA）和72例AdCC的人AdCC组织芯片进行免疫组织化学染色分析。结果表明，AGR2与Ki-67、转化生长因子β1（TGF-β1）和CD147显著相关，在人涎腺AdCC组织中显著升高。敲低AGR2显著抑制人SACC-83和SACC-LM细胞系的增殖和迁移。此外，AGR2沉默明显逆转了TGF-β1诱导的EMT现象。综上所述，我们目前的研究揭示了AGR2在AdCC中的潜在促转移作用，表明AGR2可能是具有远处转移的AdCC的一个新的治疗靶点。
