氨肽酶P2作为恶性肿瘤转移分子标志及其促进宫颈癌转移作用机制研究

项目名称： 氨肽酶P2作为恶性肿瘤转移分子标志及其促进宫颈癌转移作用机制研究

项目编号： No.81472444

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 奚玲

作者单位： 华中科技大学

项目金额： 78万元

中文摘要： 我们用细菌鞭毛肽库成功筛选到高转移肿瘤靶向肽TMTP1，并进一步筛选和鉴定出其潜在受体氨肽酶p2（XPNPEP2），初步的研究显示XPNPEP2在乳腺癌、宫颈癌等癌旁和淋巴结转移灶中高表达，放射性核素鍀99标记TMTP1可对高转移宫颈癌裸鼠皮下瘤进行分子显像，XPNPEP2作为一种针对脯氨酸残基的水解酶和肿瘤转移靶向肽TMTP1的潜在受体,是否参与促进肿瘤转移及其分子机制值得深入研究。本项目拟从妇科最常见的宫颈癌入手，大量收集样本研究宫颈癌等原发灶和转移灶中XPNPEP2表达情况，明确XPNPEP2能否作为宫颈癌乃至多种恶性肿瘤转移的一种新的分子标志，研究其是否通过促进肿瘤细胞EMT和水解肿瘤细胞外基质中粘附蛋白参与肿瘤转移，并在此基础上，对高表达XPNPEP2的宫颈癌小鼠脚垫淋巴结转移模型中，用TMTP1偶联的阿霉素进行靶向治疗，观察其疗效和毒性。

中文关键词： C22_宫颈肿瘤；肿瘤转移；氨肽酶P2

英文摘要： We have screened a novel tumor-homing peptide named TMTP1, which specifically targets metastasis, using FliTrx bacterial display system in our previous study. Furthermore, XPNPEP2 also has been screened and identified as the receptor of TMTP1 in our team (data to be published). Our primary results demonstrated that XPNPEP2 expressed at higher level in metastatic cancer cells of para-cancer nest or lymph nodes compared with that in primary cancer cells. In addition, 99mTC-HYNIC/EDDA-TMTP1 successfully targeted highly metastasis as a radiopharmaceutic imaging agent of highly metastatic cervical cancer xenograft in nude mice. The expression profile of XPNPEP2 in malignant primary and metastatic sites needs to be further investigated as a potent receptor of TMTP1 and aminopeptidase. Moreover, whether it participate in promoting tumor metastasis or its mechanisms, also needs further investigation. In this project, we planed to collect plenty of clinical primary and metastatic cervical caner samples and evaluate the expression levels of XPNPEP2, to exemplify whether it could serve as a novel tumor metastasis marker. Next, we would investigate whether XPNPEP2 promotes tumor metastasis through EMT or it degrades ECM of tumor cells. Finally, a novel drug, doxorubicin -TMTP1 would be synthesized and evaluated its targeting cytoxity and biodistribution in a cervical cancer bearing SCID mice model.

英文关键词： cervical cancer;tumor metastasis;Aminopeptidase P2;XPNPEP2