Differential reprogramming of breast cancer subtypes in 3D cultures and implications for sensitivity to targeted therapy

Esmee Koedoot*, Liesanne Wolters, Marcel Smid, Peter Stoilov, Gerhard A. Burger, Bram Herpers, Kuan Yan, Leo S. Price, John W.M. Martens, Sylvia E. Le Dévédec, Bob van de Water

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Scopus)

Abstract

Screening for effective candidate drugs for breast cancer has shifted from two-dimensional (2D) to three-dimensional (3D) cultures. Here we systematically compared the transcriptomes of these different culture conditions by RNAseq of 14 BC cell lines cultured in both 2D and 3D conditions. All 3D BC cell cultures demonstrated increased mitochondrial metabolism and downregulated cell cycle programs. Luminal BC cells in 3D demonstrated overall limited reprogramming. 3D basal B BC cells showed increased expression of extracellular matrix (ECM) interaction genes, which coincides with an invasive phenotype not observed in other BC cells. Genes downregulated in 3D were associated with metastatic disease progression in BC patients, including cyclin dependent kinases and aurora kinases. Furthermore, the overall correlation of the cell line transcriptome to the BC patient transcriptome was increased in 3D cultures for all TNBC cell lines. To define the most optimal culture conditions to study the oncogenic pathway of interest, an open source bioinformatics strategy was established.

Original languageEnglish
Article number7259
JournalScientific Reports
Volume11
Issue number1
DOIs
Publication statusPublished - 31 Mar 2021

Bibliographical note

Funding Information:
This project was supported by the European Commission ERC Advanced grant Triple-BC (Grant No. 322737) and ZonMW (Grant No. 435002025).

Publisher Copyright:
© 2021, The Author(s).

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