Han Zheng, Zhou Zhuxian, Shi Xiaoyue, Wang Junpeng, Wu Xiaohui, Sun Da, Chen Yinghua, Zhu Hui, Magi-Galluzzi Cristina, Lu Zheng-Rong
†Department of Biomedical Engineering and ‡Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106, United States.
§Glickman Urological Institute, and ∥Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44106, United States.
Bioconjug Chem. 2015 May 20;26(5):830-8. doi: 10.1021/acs.bioconjchem.5b00178. Epub 2015 Apr 15.
Extradomain-B fibronectin (EDB-FN), one of the oncofetal fibronectin (onfFN) isoforms, is a high-molecular-weight glycoprotein that mediates cell adhesion and migration. The expression of EDB-FN is associated with a number of cancer-related biological processes such as tumorigenesis, angiogenesis, and epithelial-to-mesenchymal transition (EMT). Here, we report the development of a small peptide specific to EDB-FN for targeting prostate cancer. A cyclic nonapeptide, CTVRTSADC (ZD2), was identified using peptide phage display. A ZD2-Cy5 conjugate was synthesized to accomplish molecular imaging of prostate cancer in vitro and in vivo. ZD2-Cy5 demonstrated effective binding to up-regulated EDB-FN secreted by TGF-β-induced PC3 cancer cells following EMT. Following intravenous injections, the targeted fluorescent probe specifically bound to and delineated PC3-GFP prostate tumors in nude mice bearing the tumor xenografts. ZD2-Cy5 also showed stronger binding to human prostate tumor specimens with a higher Gleason score (GS9) compared to those with a lower score (GS 7), with no binding in benign prostatic hyperplasia (BPH). Thus, the ZD2 peptide is a promising strategy for molecular imaging and targeted therapy of prostate cancer.
域外B型纤连蛋白（EDB-FN）是癌胚纤连蛋白（onfFN）的亚型之一，是一种介导细胞黏附和迁移的高分子量糖蛋白。EDB-FN的表达与许多癌症相关的生物学过程有关，如肿瘤发生、血管生成和上皮-间质转化（EMT）。在此，我们报告了一种针对EDB-FN的小肽用于靶向前列腺癌的研发情况。使用肽噬菌体展示技术鉴定出一种环九肽CTVRTSADC（ZD2）。合成了ZD2-Cy5偶联物以完成前列腺癌的体外和体内分子成像。ZD2-Cy5显示出与EMT后由TGF-β诱导的PC3癌细胞分泌的上调EDB-FN有效结合。静脉注射后，靶向荧光探针特异性结合并勾勒出荷瘤裸鼠体内的PC3-GFP前列腺肿瘤。与Gleason评分较低（GS7）的人前列腺肿瘤标本相比，ZD2-Cy5与Gleason评分较高（GS9）的标本也显示出更强的结合，在良性前列腺增生（BPH）中无结合。因此，ZD2肽是一种用于前列腺癌分子成像和靶向治疗的有前景的策略。
