Fluorescent glycan nanoparticle-based FACS assays for the identification of genuine drug-resistant cancer cells with differentiation potential

Chenglong Wang, Wencai Guan, Rong Chen, Yael Levi-Kalisman, Yichun Xu, Liwen Zhang, Min Zhou*, Guoxiong Xu*, Hongjing Dou*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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. [Figure not available: see fulltext.].

Original languageEnglish
Pages (from-to)3110-3122
Number of pages13
JournalNano Research
Volume13
Issue number11
DOIs
StatePublished - 1 Nov 2020

Bibliographical note

Publisher Copyright:
© 2020, Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature.

Keywords

  • FACS assays
  • diagnose
  • drug resistance
  • glycan nanoparticle
  • tumor heterogeneity

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