Faculty of Biotechnology, University of Wroclaw, Tamka 2, 50-137 Wroclaw, Poland.
Biochem Biophys Res Commun. 2012 Mar 9;419(2):250-5. doi: 10.1016/j.bbrc.2012.02.003. Epub 2012 Feb 8.
S100A7 (psoriasin) is a calcium-binding protein that is upregulated in many types of cancer and often associated with poor prognosis. Its role in carcinogenesis has been associated with the stimulation of VEGF and EGF activity. The recent research showed that psoriasin directly interacts with αvβ6 integrin, a protein related to the invasive phenotype of cancer. Moreover, this interaction promotes the αvβ6-dependent invasive activity. The important function of S100A7 in carcinoma development determines a great need for valuable tools enabling its detection, quantification and also activity inhibition. Here, we show the selection of S100A7 specific antibody fragments from the human scFv phage library ETH-2 Gold. We have selected antibody fragments specific for psoriasin, purified them and analyzed by BIAcore affinity measurements. The best clone was subjected to affinity maturation procedure yielding molecule with a subnanomolar affinity towards human S100A7 protein. Selected clone was expressed in a bivalent format and applied for immunostaining analysis, which confirmed the ability of the antigen recognition in physiological conditions. We therefore propose that obtained antibody, that is the first phage display-derived human antibody against psoriasin, can serve as a useful psoriasin binding platform in research, diagnostics and therapy of cancer.
S100A7（银屑病相关蛋白）是一种钙结合蛋白，在许多类型的癌症中上调，通常与预后不良有关。其在致癌作用中的作用与刺激 VEGF 和 EGF 活性有关。最近的研究表明，银屑病相关蛋白可直接与αvβ6 整合素相互作用，αvβ6 整合素与癌症的侵袭表型有关。此外，这种相互作用促进了依赖于αvβ6 的侵袭活性。S100A7 在癌发生发展中的重要功能决定了非常需要有价值的工具来实现其检测、定量和活性抑制。在这里，我们展示了从人类 scFv 噬菌体文库 ETH-2 Gold 中筛选 S100A7 特异性抗体片段。我们已经筛选出了针对银屑病相关蛋白的抗体片段，对其进行了纯化，并通过 BIAcore 亲和力测量进行了分析。最佳克隆进行了亲和力成熟过程，得到了对人 S100A7 蛋白具有亚纳摩尔亲和力的分子。选择的克隆以二价形式表达，并应用于免疫染色分析，该分析证实了在生理条件下识别抗原的能力。因此，我们提出，所获得的抗体，即第一个针对银屑病相关蛋白的噬菌体展示衍生的人抗体，可以作为研究、诊断和癌症治疗中有用的银屑病相关蛋白结合平台。
