Department of Nanomedicine, Houston Methodist Research Institute , Houston, Texas 77030, United States.
Department of Cell and Developmental Biology, Weill Medical College of Cornell University , New York, New York 10065, United States.
ACS Appl Mater Interfaces. 2017 Jul 12;9(27):22143-22148. doi: 10.1021/acsami.7b03728. Epub 2017 Jun 29.
The interaction between tumor cells and microenvironment during metastasis is mediated by the binding of cell surface receptors, such as integrins and selectins, with protein ligands. Delineation of their binding interaction and identification of key receptors may be particularly important both in understanding extracellular matrix (ECM) remodeling and in developing potential therapeutic targets. Here we present a microfluidic chip that allows qualitative and quantitative mapping of a large population cell-protein interactions. It was found that β1 integrin showed stronger binding interaction with collagen than with other ECM proteins. The upregulated β1 integrin in invasive cancer cells enhanced cell-ECM interaction and may promote ECM remodeling. Cancer cells also showed strong interaction with plasma fibrinogen, the elevated level of which may help cancer cells arrest on blood vessels. We also verified that the chip may provide a platform for drug discovery by targeting integrins and cytoskeletons.
肿瘤细胞与微环境在转移过程中的相互作用是通过细胞表面受体(如整合素和选择素)与蛋白配体的结合来介导的。阐明它们的结合相互作用并确定关键受体可能在理解细胞外基质(ECM)重塑和开发潜在的治疗靶点方面特别重要。在这里,我们展示了一种微流控芯片,它可以定性和定量地绘制大量细胞-蛋白相互作用图谱。结果发现,β1 整合素与胶原蛋白的结合相互作用强于与其他 ECM 蛋白的结合相互作用。侵袭性癌细胞中上调的β1 整合素增强了细胞-ECM 的相互作用,并可能促进 ECM 重塑。癌细胞与血浆纤维蛋白原也表现出强烈的相互作用,其水平升高可能有助于癌细胞在血管上停滞。我们还验证了该芯片可通过靶向整合素和细胞骨架为药物发现提供平台。