Department of Neurosurgery, Xiangya Hospital, Central South University; 87 Xiangya Road, Changsha, Hunan, 410078, P.R. China.
Department of Medicine, University of Oklahoma Health Science Center; 975NE, 10th ST, Oklahoma City, Oklahoma, 73104, United States.
Sci Rep. 2017 Dec 13;7(1):17523. doi: 10.1038/s41598-017-17679-2.
Non-functioning pituitary adenomas (NFPAs) are the most frequent pituitary tumors. The elucidation of the mechanisms of aggressive NFPAs in bone destruction is required in order to guide the clinical diagnosis and treatment of NFPAs. In the present study, we investigated the differential proteomics of fibroblasts isolated from clinical specimens of NFPAs with or without bone destruction. Proteomic analysis revealed a group of molecules associated with cytoskeleton organization, including caldesmon, were differentially expressed between fibroblasts isolated from bone destruction NFPAs (BD-NFPAs) and fibroblasts isolated from non-bone destruction NFPAs (NBD-NFPAs). The secreted proteins analysis found that osteopontin was significantly upregulated in BD-NFPAs fibroblasts. Furthermore, immunohistochemical staining of the NFPAs clinical samples showed that the expression of caldesmon in stromal cells and the expression of osteopontin in both tumor cells and stroma were significantly increased in BD-NFPAs. Taken together, our results indicate a possible way that osteopontin secreted from both NFPA cells and surrounding fibroblasts modify caldesmon expression and polymerization in fibroblasts, which may contribute to bone destruction in NFPA patients.
无功能垂体腺瘤（NFPA）是最常见的垂体肿瘤。为了指导 NFPA 的临床诊断和治疗，需要阐明导致 NFPA 发生侵袭性骨破坏的机制。在本研究中，我们研究了伴有或不伴有骨破坏的 NFPA 临床标本中分离的成纤维细胞的差异蛋白质组学。蛋白质组学分析显示，一组与细胞骨架组织相关的分子，包括钙调蛋白，在骨破坏 NFPA（BD-NFPA）和成纤维细胞与非骨破坏 NFPA（NBD-NFPA）分离的成纤维细胞之间存在差异表达。分泌蛋白分析发现，BD-NFPA 成纤维细胞中骨桥蛋白的表达显著上调。此外，NFPA 临床样本的免疫组织化学染色显示，BD-NFPA 中基质细胞中钙调蛋白的表达以及肿瘤细胞和基质中骨桥蛋白的表达均显著增加。综上所述，我们的研究结果表明，骨桥蛋白可能通过 NFPA 细胞和周围成纤维细胞分泌，改变成纤维细胞中钙调蛋白的表达和聚合，从而促进 NFPA 患者的骨质破坏。
