肿瘤侵袭是造成垂体腺瘤手术无法根除，导致复发和影响预后的关键因素。EMT是肿瘤侵袭的早期事件和关键环节。我们前期发现ADAM12高表达促进垂体腺瘤侵袭。通过进一步预实验，我们发现上调ADAM12表达，垂体腺瘤细胞出现明显的EMT现象(E-cadherin下调，N-cadherin、Fibronectin上调)。这些结果提示ADAM12能够诱导垂体腺瘤细胞发生EMT促进肿瘤侵袭，然而，其潜在调控机制尚未阐明。利用蛋白芯片筛选我们发现EphB2可能是ADAM12的作用靶点。结合文献报道EphB2信号通路在肿瘤细胞EMT中发挥重要作用。基于此，本项目拟以人垂体腺瘤组织，体外细胞和体内动物为实验对象，采用分子生物学和药物干预等手段，探讨ADAM12调控EphB2信号通路在诱导垂体腺瘤细胞EMT中的作用和分子机制。本项目的完成有望为侵袭性垂体腺瘤提供一个全新的生物标志物和治疗靶点。

Accumulative studies elucidated that tumor invasion of pituitary adenomas was associated with incomplete tumor resection, tumor recurrence and poor prognosis. Epithelial-mesenchymal transition (EMT) is the initial period and key procedure of tumor invasion. We previously reported that the over-expression of a disintegrin and metalloproteinase 12 (ADAM12) contributed to tumor invasion of pituitary adenomas. A significant EMT phenomenon of pituitary adenoma cells came into sight after ADAM12 up-regulation, which indicated that ADAM12 could induce EMT to promote tumor invasion in pituitary adenomas. However, the potential mechanism has been largely elusive. By employing RTK Phosphorylation Antibody Array, we found that EphB2 might be the target of ADAM12 in pituitary adenomas. Numerous evidence demonstrated that EphB2 signaling pathway plays an important role in EMT. Therefore, this project is to explore the impact of ADAM12 on pituitary adenoma cell EMT in vitro and in vivo, and to address the potential mechanism of ADAM12 regulating EphB2 signaling pathway and its role in pituitary adenoma cell EMT at both molecular and functional levels. This novel study may provide the evidence for defining ADAM12 as a new biomarker and therapeutic target for invasive pituitary adenomas.