Hu Shengjuan, Guo Xinning, Xie Huahong, Du Yulei, Pan Yanglin, Shi Yongquan, Wang Jun, Hong Liu, Han Shuang, Zhang Dongtao, Huang Dawei, Zhang Kedong, Bai Feihu, Jiang Haiping, Zhai Huihong, Nie Yongzhan, Wu Kaichun, Fan Daiming
State Key Laboratory of GI Cancer Biology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shanxi Province 710032, PR China.
Biochem Biophys Res Commun. 2006 Mar 24;341(4):964-72. doi: 10.1016/j.bbrc.2006.01.047. Epub 2006 Jan 24.
Organ-specific metastasis is an important character of cancer cells. Cancer cells that can metastasize to a special organ were thought to have different proteins in cell membrane, which might have potential utility as diagnostic markers and therapeutic targets. In the present work, based on high liver-metastatic gastric cancer cells, XGC9811-L, a screening approach with phage displayed peptide library, was successfully used to isolate 8-mer peptide ligands binding to the target cells. The phage20 had the highest binding efficiency to XGC9811-L cells, which also displayed remarkable cell specificity. Peptide20 that was displayed on phage20 could suppress the motility and invasion of XGC9811-L significantly. The adhesive ability of XGC9811-L to collagen IV was also inhibited by peptide20. Furthermore, phage20 could significantly reduce the incidence of liver metastasis of gastric cancer transplanted into nude mice and was also beneficial for the reduction the number of metastatic nodules in the liver. In conclusion, the phage display is an effective method to screen for the new molecules associated with organ-specific metastasis. The selected peptide20 can reverse the liver metastasis behavior of the gastric cancer cells.
器官特异性转移是癌细胞的一个重要特征。能够转移至特定器官的癌细胞被认为在细胞膜上具有不同的蛋白质,这些蛋白质可能具有作为诊断标志物和治疗靶点的潜在用途。在本研究中,基于高肝转移潜能的胃癌细胞XGC9811-L,采用噬菌体展示肽库筛选方法成功分离出与靶细胞结合的8肽配体。噬菌体20对XGC9811-L细胞具有最高的结合效率,且表现出显著的细胞特异性。展示在噬菌体20上的肽20能够显著抑制XGC9811-L的运动性和侵袭能力。肽20还能抑制XGC9811-L与IV型胶原的黏附能力。此外,噬菌体20能够显著降低移植到裸鼠体内的胃癌的肝转移发生率,并且有利于减少肝脏中转移瘤结节的数量。总之,噬菌体展示是筛选与器官特异性转移相关新分子的有效方法。所筛选出的肽20能够逆转胃癌细胞的肝转移行为。