Multi-Drug-Resistance in Drug-Naive and Drug-Exposed Ovarian Cancer Cells Responds Differently to Cell Culture Dimensionality

Does cell clustering in ovarian cancer influence intrinsic and acquired multi-drug resistance (MDR) differently? To address this question, we studied cultured monolayers (representing individual cells) and cultured spheroids (representing clusters) formed by drug-naive (intrinsic MDR) and drug-expos...

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Bibliographic Details
Published inbioRxiv
Main Authors Koshkin, Vasilij, Mariana Bleker De Oliveira, Peng, Chun, Ailles, Laurie E, Liu, Geoffrey, Covens, Allan, Krylov, Sergey N
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 29.07.2020
Subjects
Cell culture
Cell number
Cytometry
Drug resistance
Multidrug resistance
Ovarian cancer
Spheroids
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Summary:Does cell clustering in ovarian cancer influence intrinsic and acquired multi-drug resistance (MDR) differently? To address this question, we studied cultured monolayers (representing individual cells) and cultured spheroids (representing clusters) formed by drug-naive (intrinsic MDR) and drug-exposed (acquired MDR) lines of ovarian cancer A2780 cells by cytometry of reaction rate constant (CRRC). MDR efflux was characterized by accurate and robust "cell number vs. MDR efflux rate constant (kMDR)" histograms. Both drug-naive and drug-exposed monolayer cells presented unimodal histograms; the histogram of drug-exposed cells was shifted towards higher kMDR value suggesting greater MDR activity. Spheroids of drug-naive cells presented a bimodal histogram indicating the presence of two subpopulations with different MDR activity. In contrast, spheroids of drug-exposed cells presented a unimodal histogram qualitatively similar to that of the monolayers of drug-exposed cells but with a moderate shift towards greater MDR activity. The observed greater effect of cell clustering on intrinsic than on acquired MDR can help guide the development of new therapeutic strategies targeting clusters of circulating tumor cells. Competing Interest Statement The authors have declared no competing interest. Footnotes * Figures 1 and 2 were added as well as supporting information with source data containing microscopy images and data extracted from these images to build kinetics traces of MDR-driven extrusion from single cells
DOI:10.1101/2020.07.12.199125