Transcriptional Landscape of 3D vs. 2D Ovarian Cancer Cell Models

Rachel Kerslake, Birhanu Belay, Suzana Panfilov, Marcia Hall, Ioannis Kyrou, Harpal S. Randeva, Jari Hyttinen, Emmanouil Karteris, Cristina Sisu

Research output: Contribution to journalArticlepeer-review


Three-dimensional (3D) cancer models are revolutionising research, allowing for the recapitulation of an in vivo-like response through the use of an in vitro system, which is more complex and physiologically relevant than traditional monolayer cultures. Cancers such as ovarian (OvCa) are prone to developing resistance, are often lethal, and stand to benefit greatly from the enhanced modelling emulated by 3D cultures. However, the current models often fall short of the predicted response, where reproducibility is limited owing to the lack of standardised methodology and established protocols. This meta-analysis aims to assess the current scope of 3D OvCa models and the differences in the genetic profiles presented by a vast array of 3D cultures. An analysis of the literature ( spanning 2012–2022 was used to identify studies with paired data of 3D and 2D monolayer counterparts in addition to RNA sequencing and microarray data. From the data, 19 cell lines were found to show differential regulation in their gene expression profiles depending on the bio-scaffold (i.e., agarose, collagen, or Matrigel) compared to 2D cell cultures. The top genes differentially expressed in 2D vs. 3D included C3, CXCL1, 2, and 8, IL1B, SLP1, FN1, IL6, DDIT4, PI3, LAMC2, CCL20, MMP1, IFI27, CFB, and ANGPTL4. The top enriched gene sets for 2D vs. 3D included IFN-α and IFN-γ response, TNF-α signalling, IL-6-JAK-STAT3 signalling, angiogenesis, hedgehog signalling, apoptosis, epithelial–mesenchymal transition, hypoxia, and inflammatory response. Our transversal comparison of numerous scaffolds allowed us to highlight the variability that can be induced by these scaffolds in the transcriptional landscape and identify key genes and biological processes that are hallmarks of cancer cells grown in 3D cultures. Future studies are needed to identify which is the most appropriate in vitro/preclinical model to study tumour microenvironments.
Original languageEnglish
Article number3350
Number of pages21
Issue number13
Early online date26 Jun 2023
Publication statusPublished - 26 Jun 2023

Bibliographical note

Copyright © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (

This study was funded through the Cancer Treatment and Research Trust and the University Hospitals Coventry and Warwickshire NHS Trust (grant no. 12899).


  • 2D
  • 3D
  • Matrigel
  • agarose
  • collagen
  • extracellular matrix (ECM)
  • high-grade serous ovarian cancer (HGSOC)
  • monolayer
  • ovarian cancer
  • scaffold
  • tumour microenvironment (TME)


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