Multicellular tumor spheroids bridge the gap between two-dimensional cancer cells and solid tumors: The role of lipid metabolism and distribution

Peisi Xie, Jinghui Zhang, Pengfei Wu, Yongjiang Wu, Yanjun Hong, Jianing Wang, Zongwei Cai*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

15 Citations (Scopus)


Previous studies demonstrated that three-dimensional (3D) multicellular tumor spheroids (MCTS) could more closely mimic solid tumors than two-dimensional (2D) cancer cells in terms of the spatial structure, extracellular matrix-cell interaction, and gene expression pattern. However, no study has been reported on the differences in lipid metabolism and distribution among 2D cancer cells, MCTS, and solid tumors. Here, we used HepG2 liver cancer cell lines to establish these three cancer models. The variations of lipid profiles and spatial distribution among them were explored by using mass spectrometry-based lipidomics and matrix-assisted laser desorption/ionization mass spectrometry imaging (MSI). The results revealed that MCTS, relative to 2D cells, had more shared lipid species with solid tumors. Furthermore, MCTS contained more comparable characteristics than 2D cells to solid tumors with respect to the relative abundance of most lipid classes and mass spectra patterns. MSI data showed that 46 of 71 lipids had similar spatial distribution between solid tumors and MCTS, while lipids in 2D cells had no specific spatial distribution. Interestingly, most of detected lipid species in sphingolipids and glycerolipids preferred locating in the necrotic region to the proliferative region of solid tumors and MCTS. Taken together, our study provides the evidence of lipid metabolism and distribution demonstrating that MCTS are a more suitable in vitro model to mimic solid tumors, which may offer insights into tumor metabolism and microenvironment.

Original languageEnglish
Article number107349
JournalChinese Chemical Letters
Issue number2
Early online date19 Mar 2022
Publication statusPublished - Feb 2023

Scopus Subject Areas

  • Chemistry(all)

User-Defined Keywords

  • Lipid distribution
  • Lipid metabolism
  • Solid tumors
  • Three-dimensional cell spheroids
  • Two-dimensional cells


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