Multifunctional profiling of triple-negative breast cancer patient-derived tumoroids for disease modeling.

Autor:	Cromwell EF; Protein Fluidics, Inc., USA. Electronic address: ecromwell@proteinfluidics.com., Sirenko O; Molecular Devices, LLC, USA., Nikolov E; Protein Fluidics, Inc., USA., Hammer M; Molecular Devices, LLC, USA., Brock CK; Tulane University School of Medicine, USA., Matossian MD; Tulane University School of Medicine, USA., Alzoubi MS; Tulane University School of Medicine, USA., Collins-Burow BM; Tulane University School of Medicine, USA., Burow ME; Tulane University School of Medicine, USA.
Jazyk:	angličtina
Zdroj:	SLAS discovery : advancing life sciences R & D [SLAS Discov] 2022 Apr; Vol. 27 (3), pp. 191-200. Date of Electronic Publication: 2022 Feb 04.
DOI:	10.1016/j.slasd.2022.01.006
Abstrakt:	3D cell models derived from patient tumors are highly translational tools that can recapitulate the complex genetic and molecular compositions of solid cancers and accelerate identification of drug targets and drug testing. However, the complexity of performing assays with such models remains a hurdle for their wider adoption. In the present study, we describe methods for processing and multi-functional profiling of tumoroid samples to test compound effects using a novel flowchip system in combination with high content imaging and metabolite analysis. Tumoroids were formed from primary cells isolated from a patient-derived tumor explant, TU-BcX-4IC, that represents metaplastic breast cancer with a triple-negative breast cancer subtype. Assays were performed in a microfluidics-based device (Pu⋅MA System) that allows automated exchange of media and treatments of tumoroids in a tissue culture incubator environment. Multi-functional assay profiling was performed on tumoroids treated with anti-cancer drugs. High-content imaging was used to evaluate drug effects on cell viability and expression of E-cadherin and CD44. Lactate secretion was used to measure tumoroid metabolism as a function of time and drug concentration. Observed responses included loss of cell viability, decrease in E-cadherin expression, and increase of lactate production. Importantly, the tumoroids were sensitive to romidepsin and trametinib, while showed significantly reduced sensitivity to paclitaxel and cytarabine, consistent with the primary tumor response. These methods for multi-parametric profiling of drug effects in patient-derived tumoroids provide an in depth understanding of drug sensitivity of individual tumor types, with important implications for the future development of personalized medicine. Competing Interests: Declaration of Competing Interest The authors declared the following potential competing interests with respect to the research, authorship, and/or publication of this article: The authors EFC and EN are employed by Protein Fluidics, which manufactures the PuMA System. The authors OS and MH are employed by Molecular Devices, which manufactures the ImageXpress Micro Confocal system. The authors CKB, MDM, MSA, BMC-B, and MEB declare no competing interests. This article is being reproduced in print post-publication in a sponsored print collection for distribution. The company sponsoring the print collection was not involved in the editorial selection or review of this article. (Copyright © 2022. Published by Elsevier Inc.)
Databáze:	MEDLINE
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