Chen Si, Le Thien, Harley Brendan A C, Imoukhuede P I
Department of Bioengineering, University of Illinois at Urbana-Champaign, Champaign, IL, United States.
Department of Mathematics and Department of Computer Science, University of Illinois at Urbana-Champaign, Champaign, IL, United States.
Front Bioeng Biotechnol. 2018 Jul 11;6:92. doi: 10.3389/fbioe.2018.00092. eCollection 2018.
Dysregulation of tyrosine kinase receptor (RTK) signaling pathways play important roles in glioblastoma (GBM). However, therapies targeting these signaling pathways have not been successful, partially because of drug resistance. Increasing evidence suggests that tumor heterogeneity, more specifically, GBM-associated stem and endothelial cell heterogeneity, may contribute to drug resistance. In this perspective article, we introduce a high-throughput, quantitative approach to profile plasma membrane RTKs on single cells. First, we review the roles of RTKs in cancer. Then, we discuss the sources of cell heterogeneity in GBM, providing context to the key cells directing resistance to drugs. Finally, we present our provisionally patented qFlow cytometry approach, and report results of a "proof of concept" patient-derived xenograft GBM study.
酪氨酸激酶受体(RTK)信号通路的失调在胶质母细胞瘤(GBM)中起着重要作用。然而,针对这些信号通路的治疗尚未取得成功,部分原因是耐药性。越来越多的证据表明,肿瘤异质性,更具体地说,GBM相关的干细胞和内皮细胞异质性,可能导致耐药性。在这篇观点文章中,我们介绍了一种高通量、定量的方法来分析单细胞上的质膜RTK。首先,我们回顾RTK在癌症中的作用。然后,我们讨论GBM中细胞异质性的来源,为指导耐药性的关键细胞提供背景信息。最后,我们展示了我们暂时获得专利的q流式细胞术方法,并报告了一项“概念验证”患者来源的异种移植GBM研究的结果。