Noori Mahboubeh S, Streator Evan S, Carlson Grady E, Drozek David S, Burdick Monica M, Goetz Douglas J
Department of Chemical and Biomolecular Engineering, Ohio University, Athens, Ohio 45701, USA.
Integr Biol (Camb). 2018 Dec 19;10(12):747-757. doi: 10.1039/c8ib00132d.
Esophageal cancer has a 5 year survival rate of ∼20%. This dismal prognosis is due, in part, to the fact that esophageal cancer often presents at a late stage. Thus, there is a critical need for assays that enable the early detection of cancerous tissue within the esophagus. The luminal surface of the esophagus expresses signature molecule(s) at sites of transformation providing an avenue for the development of in situ assays that detect neoplastic growth within the esophagus. An attractive approach, receiving increased attention, is the endoscopic administration of particles conjugated with ligands to signature molecules present on transforming tissue. Detection of the particles within the esophagus, post-washing, would indicate the presence of the signature molecule and thus transforming tissue. In this work, we utilized cancerous and normal esophageal cells to provide in vitro proof of principle for this approach utilizing ligand-conjugated microspheres and demonstrate the need, and provide the framework for, engineering this technology. Specifically, the study (i) reveals selective increased expression of signature molecules on cancerous esophageal cells relative to normal cells; (ii) demonstrates selective binding of ligand-conjugated microspheres to cancerous esophageal cells relative to normal cells; (iii) demonstrates that the selective recognition of cancerous, relative to normal esophageal cells, is highly dependent on the biophysical design of the assay; and (iv) advocates utilizing the knowledge from the field of cell adhesion as a guide for the effective development of ligand-conjugated particle-based schemes that seek to detect esophageal oncogenesis in situ.
食管癌的5年生存率约为20%。这种令人沮丧的预后部分归因于食管癌往往在晚期才出现。因此,迫切需要能够早期检测食管内癌组织的检测方法。食管的腔内表面在转化部位表达标志性分子,这为开发检测食管内肿瘤生长的原位检测方法提供了途径。一种受到越来越多关注的有吸引力的方法是通过内镜将与标志性分子配体偶联的颗粒施用于转化组织上。冲洗后在食管内检测到颗粒将表明存在标志性分子,从而表明存在转化组织。在这项工作中,我们利用癌细胞和正常食管细胞为这种使用配体偶联微球的方法提供体外原理验证,并证明了设计这项技术的必要性并提供了框架。具体而言,该研究(i)揭示了与正常细胞相比,癌性食管细胞上标志性分子的选择性表达增加;(ii)证明了与正常细胞相比,配体偶联微球与癌性食管细胞的选择性结合;(iii)表明相对于正常食管细胞,对癌性细胞的选择性识别高度依赖于检测方法的生物物理设计;(iv)主张利用细胞黏附领域的知识作为指导,有效开发旨在原位检测食管肿瘤发生的基于配体偶联颗粒的方案。