Aggarwal Saurabh, Janssen Samuel, Wadkins Randy M, Harden James L, Denmeade Samuel R
The Johns Hopkins University School of Medicine, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21231, USA.
Biomaterials. 2005 Oct;26(30):6077-86. doi: 10.1016/j.biomaterials.2005.03.040.
Early detection is critical in the administration of definitive and curative therapy of cancer. However, current detection methods are ineffective at identifying the presence of circulating metastatic cancer cells in the blood because they typically sample only a relatively small volume of blood. One strategy for sampling larger blood volumes would be to capture circulating cells in vivo over an extended period of time. The development of such a method would be substantially facilitated by the identification of peptide ligands that bind selectively to metastatic cancer cells in the blood with high affinity. To identify such ligands a combinatorial peptide library was synthesized on polyethylene acrylamide (PEGA) resin and screened for binding to malignant epithelial cells. Using Biacore, cell binding assays were performed to demonstrate that peptides selected from PEGA bead screen can bind selectively to malignant epithelial cancer cells and not to circulating leukocytes under physiologic shear stress conditions. One peptide, with the sequence QMARIPKRLARH, was used to demonstrate selective labeling of malignant epithelial cells spiked in whole blood. When immobilized on appropriate surfaces, these peptides could be used in both in vivo and ex vivo cell separation devices to efficiently and selectively capture metastatic epithelial cancer cells from flowing blood.
早期检测对于癌症的确定性和治愈性治疗至关重要。然而，目前的检测方法在识别血液中循环转移性癌细胞的存在方面效果不佳，因为它们通常只采集相对少量的血液样本。一种采集更大血量的策略是在较长时间内体内捕获循环细胞。鉴定与血液中转移性癌细胞具有高亲和力且选择性结合的肽配体将极大地促进这种方法的开发。为了鉴定此类配体，在聚丙烯酰胺（PEGA）树脂上合成了一个组合肽库，并筛选其与恶性上皮细胞的结合情况。使用Biacore进行细胞结合测定，以证明从PEGA珠筛选中选出的肽在生理剪切应力条件下可选择性结合恶性上皮癌细胞，而不结合循环白细胞。一种序列为QMARIPKRLARH的肽被用于证明在全血中掺入的恶性上皮细胞的选择性标记。当固定在合适的表面上时，这些肽可用于体内和体外细胞分离装置，以从流动血液中高效且选择性地捕获转移性上皮癌细胞。
