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3D spheroid culture to examine adaptive therapy response in invading tumor cells.

Published version
Peer-reviewed

Repository DOI


Type

Article

Change log

Authors

Atlasy, Nader 
van Reijmersdal, Vince 
Stunnenberg, Henk 
Hulsbergen-Veelken, Cornelia 

Abstract

UNLABELLED: 3D in vitro culture models of cancer cells in extracellular matrix (ECM) have been developed to investigate drug targeting and resistance or, alternatively, mechanisms of invasion; however, models allowing analysis of shared pathways mediating invasion and therapy resistance are lacking. To evaluate therapy response associated with cancer cell invasion, we here used 3D invasion culture of tumor spheroids in 3D fibrillar collagen and applied Ethanol-Ethyl cinnamate (EtOH-ECi) based optical clearing to detect both spheroid core and invasion zone by subcellular-resolved 3D microscopy. When subjected to a single dose of irradiation (4 Gy), we detected significant cell survival in the invasion zone. By physical separation of the core and invasion zone, we identified differentially regulated genes preferentially engaged in invading cells controlling cell division, repair, and survival. This imaging-based 3D invasion culture may be useful for the analysis of complex therapy-response patterns in cancer cells in drug discovery and invasion-associated resistance development. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s44164-022-00040-x.

Description

Keywords

3D matrix culture, Cancer invasion, Irradiation, Molecular profiling, RNAseq, Resistance, Spheroid, Therapy response

Journal Title

In Vitro Model

Conference Name

Journal ISSN

2731-3433
2731-3441

Volume Title

1

Publisher

Springer Science and Business Media LLC