磷酸化的OPN激活CALD聚合体的分子机制在无功能垂体腺瘤侵袭与复发中的研究

部分无功能垂体腺瘤（non-functioning pituitary adenomas，NFPA）具有类似恶性肿瘤的侵袭与复发的特性，但机制不明。我们前期研究报道：钙调蛋白结合蛋白(Caldesmon, CALD)是"侵袭伪足"的主要结构性成份；骨桥蛋白（Osteopontin, OPN） 和CALD 参与肿瘤的侵袭转移，与骨质破坏呈正相关；在NFPA的成纤维细胞中发现了OPN与CALD 结合的现象。本研究拟通过体内外实验及蛋白质组学技术，揭示OPN磷酸化的具体形式；OPN磷酸化活化后对下游效应分子（整合素αvβ3、磷脂酶Cγ、钙调蛋白)的功能调控作用；阐明CALD聚合体形成"侵袭伪足"受OPN调控作用的机制。为揭示NFPA的侵袭和复发提供理论基础和实验依据。

Part of the non-functioning pituitary adenoma (NFPA) with characteristics of invasion and recurrence are similar to the malignant tumors, however, the mechanism does not know. Our previous studies have reported that Caldesmon (CALD) is the major structural ingredient of "invadopodia". Osteopontin(OPN) and CALD involved in tumor invasion and metastasis, furthermore, associating with the bone destruction. We found the combination of OPN and CALD in NFPA fibroblasts.In this study, we use in vivo experiments and animal model, even proteomics to reveal the forms of OPN phosphorylation and the activation to downstream effector molecules (integrins αvβ3, phospholipase C?, calmodulin) functions by OPN phosphorylation. We would clarify the mechanism of CALD form into "invadopodia" by the regulation of OPN. We will provide a theoretical basis and experimental evidence by revealing the invasion and recurrence of NFPA.