Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Oncol Rep. 2016 May;35(5):2785-94. doi: 10.3892/or.2016.4667. Epub 2016 Mar 9.
A disintegrin and metalloprotease 10 (ADAM10) is involved in the tumorigenesis, invasion and metastasis of several types of solid tumors. However, the potential role of ADAM10 in human esophageal squamous cell carcinoma (ESCC) is not yet well understood. The present study showed that ADAM10 was overexpressed in human ESCC tissues in vivo, and positively associated with depth of tumor invasion, lymph node metastasis and TNM stage, contributing to tumor carcinogenesis, invasion and metastasis. Additionally, ADAM10 was overexpressed in 3 types of ESCC cell lines in vitro, as compared to that in normal esophageal epithelial cells (NEECs); and moreover, ESCC cells with high ADAM10 expression obtained enhanced invasion and migration ability. Subsequently, ADAM10 silencing by small interfering (si) RNA in ESCC cell line, EC-1, reduced cell invasion, migration and proliferation in vitro. Finally, ADAM10 negatively regulated E-cadherin in ESCC in vivo and in vitro. In conclusion, active ADAM10 promotes the carcinogenesis, invasion, metastasis and proliferation of ESCC and controls invasion and metastasis at least in part through the shedding of E-cadherin activity, which makes it a potential biomarker and a useful therapeutic target for ESCC.
解整合素金属蛋白酶 10（ADAM10）参与多种实体瘤的发生、侵袭和转移。然而，ADAM10 在人食管鳞状细胞癌（ESCC）中的潜在作用尚不清楚。本研究表明，ADAM10 在体内人 ESCC 组织中过度表达，并与肿瘤浸润深度、淋巴结转移和 TNM 分期呈正相关，有助于肿瘤发生、侵袭和转移。此外，与正常食管上皮细胞（NEECs）相比，ADAM10 在 3 种 ESCC 细胞系中过度表达；并且，ADAM10 高表达的 ESCC 细胞获得了增强的侵袭和迁移能力。随后，通过小干扰（si）RNA 在 ESCC 细胞系 EC-1 中沉默 ADAM10，降低了细胞的侵袭、迁移和增殖能力。最后，ADAM10 负调控 ESCC 中的 E-钙黏蛋白的表达。综上所述，活性 ADAM10 促进 ESCC 的发生、侵袭、转移和增殖，并通过脱落 E-钙黏蛋白活性至少部分控制侵袭和转移，使其成为 ESCC 的一个潜在的生物标志物和有用的治疗靶点。
