Fluorescent glycan nanoparticle-based FACS assays for the identification of genuine drug-resistant cancer cells with dif
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Fluorescent glycan nanoparticle-based FACS assays for the identification of genuine drug-resistant cancer cells with differentiation potential Chenglong Wang1,2, Wencai Guan2, Rong Chen3,4, Yael Levi-Kalisman5, Yichun Xu6, Liwen Zhang6, Min Zhou3,4 (), Guoxiong Xu2 (), and Hongjing Dou1 () 1
The State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China 2 Research Center for Clinical Research, Jinshan Hospital, Fudan University, Shanghai 200540, China 3 Department of Respiratory and Critical Care Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China 4 Institute of Respiratory Diseases, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China 5 The Center for Nanoscience and Nanotechnology and the Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem 91905, Israel 6 Shanghai Biochip Co. Ltd. and National Engineering Center for Biochip at Shanghai, Shanghai 201203, China © Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020 Received: 8 April 2020 / Revised: 9 July 2020 / Accepted: 10 July 2020
ABSTRACT Herein we develop a unique differentiated-uptake strategy capable of efficient and high-purity isolation of genuine drug-resistant (DR) cells from three types of drug-surviving cancer cells, which include paclitaxel-surviving human ovarian OVCAR-3 cancer cells and human lung carcinoma A549/Taxol cells, and doxorubicin-surviving human immortalized myelogenous leukemia K562/ADR cells. By using this strategy which relies on fluorescent glycan nanoparticle (FGNP)-based fluorescence-activated cell sorting (FACS) assays, two subpopulations with distinct fluorescences existing in drug-surviving OVCAR-3 cells were separated, and we found that the lower fluorescence (LF) subpopulation consisted of DR cells, while the higher fluorescence (HF) subpopulation was comprised of non-DR cells. Besides, the DR cells and their progenies were found distinct in their increased expression of drug-resistant genes. More intriguingly, by using the FGNP-based FACS assay to detect DR/non-DR phenotypes, we found that the DR phenotype had a potential to differentiate into the non-DR progeny, which demonstrates the differentiation feature of stem-like cancer cells. Further research disclosed that the assay can quantitatively detect the degree of drug resistance in DR cells, as well as the reversal of drug resistance that are tackled by various therapeutic methods. The strategy thus paves the way to develop theranostic approaches associated with chemotherapy-resistance and cancer stemness.
KEYWORDS glycan nanoparticle, FACS assays, drug resistance, tumor heterogeneity, diagnose
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Introduction
Chemotherapy is the most common treatment for tumors, but tumor cells can readily develop drug resistance [1], which is one of the important factors leading to the failure of chemotherapy and to recurrence of this disease [2]. There are some reagents
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