Citation: Peisi Xie, Jinghui Zhang, Pengfei Wu, Yongjiang Wu, Yanjun Hong, Jianing Wang, Zongwei Cai. Multicellular tumor spheroids bridge the gap between two-dimensional cancer cells and solid tumors: The role of lipid metabolism and distribution[J]. Chinese Chemical Letters, ;2023, 34(2): 107349. doi: 10.1016/j.cclet.2022.03.072 shu

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

Peisi Xie ^a ,
Jinghui Zhang ^{a, b} ,
Pengfei Wu ^a ,
Yongjiang Wu ^b ,
Yanjun Hong ^{a, c} ,
Jianing Wang ^a ,
Zongwei Cai ^{a, *,}

a.
State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China
b.
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
c.
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China

zwcai@hkbu.edu.hk

Received Date: 5 January 2022
Revised Date: 14 February 2022
Accepted Date: 16 March 2022
Available Online: 19 March 2022

Figures(4)

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.
- Lipid metabolism,
- Lipid distribution,
- Two-dimensional cells,
- Three-dimensional cell spheroids,
- Solid tumors
1. [1]
  S. Breslin, L. O'Driscoll, Drug Discov. Today 18 (2013) 240–249. doi: 10.1016/j.drudis.2012.10.003
2. [2]
  Y. Wang, A.B. Hummon, J. Biol. Chem. 297 (2021) 101139. doi: 10.1016/j.jbc.2021.101139
3. [3]
  J. Zhang, Q. Du, X. Song, et al., Theranostics 10 (2020) 2621–2630. doi: 10.7150/thno.41763
4. [4]
  T. Sonoda, H. Kobayashi, T. Kaku, et al., Cancer Lett. 196 (2003) 229–237. doi: 10.1016/S0304-3835(03)00216-7
5. [5]
  E.C. Costa, A.F. Moreira, D. de Melo-Diogo, et al., Biotechnol. Adv. 34 (2016) 1427–1441. doi: 10.1016/j.biotechadv.2016.11.002
6. [6]
  S. Nath, G.R. Devi, Pharmacol. Ther. 163 (2016) 94–108. doi: 10.1016/j.pharmthera.2016.03.013
7. [7]
  L. Xiang, L. Zhu, Y. Huang, Z. Cai, Small Methods 4 (2020) 2000160. doi: 10.1002/smtd.202000160
8. [8]
  L. Zhang, B. Zhu, Y. Zeng, et al., Cancer Lett. 470 (2020) 75–83. doi: 10.1016/j.canlet.2019.08.014
9. [9]
  L. Huang, X. Mao, C. Sun, et al., Anal. Chim. Acta 1077 (2019) 183–190. doi: 10.1016/j.aca.2019.05.068
10. [10]
  N. Vidavsky, J.A. Kunitake, M.E. Diaz-Rubio, et al., ACS Cent. Sci. 5 (2019) 768–780. doi: 10.1021/acscentsci.8b00932
11. [11]
  J. Wang, S. Qiu, S. Chen, et al., Anal. Chem. 87 (2015) 422–430. doi: 10.1021/ac504294s
12. [12]
  C. Yang, H.K. Lee, Y. Zhang, et al., Anal. Chem. 91 (2019) 8783–8788. doi: 10.1021/acs.analchem.9b00711
13. [13]
  A.R. Buchberger, N.Q. Vu, J. Johnson, K. DeLaney, L. Li, J. Am. Soc. Mass Spectrom. 31 (2020) 1058–1065. doi: 10.1021/jasms.9b00107
14. [14]
  B. Bakker, G.B. Eijkel, R.M. Heeren, et al., Anal. Chem. 89 (2017) 9438–9444. doi: 10.1021/acs.analchem.7b02265
15. [15]
  S.S. Wang, Y.J. Wang, J. Zhang, T.Q. Sun, Y.L. Guo, Anal. Chem. 91 (2019) 4070–4076. doi: 10.1021/acs.analchem.8b05680
16. [16]
  G.J. LaBonia, K.R. Ludwig, C.B. Mousseau, A.B. Hummon, Anal. Chem. 90 (2018) 1423–1430. doi: 10.1021/acs.analchem.7b04969
17. [17]
  P. Xie, C. Zhao, X. Liang, et al., Anal. Chem. 92 (2020) 7413–7418. doi: 10.1021/acs.analchem.9b05812
18. [18]
  Q. Zang, C. Sun, X. Chu, et al., Anal. Chim. Acta 1155 (2021) 338342. doi: 10.1016/j.aca.2021.338342
19. [19]
  X. Mao, J. He, T. Li, et al., Sci. Rep. 6 (2016) 1–12. doi: 10.1038/s41598-016-0001-8
20. [20]
  D.L. Dillehay, S.K. Webb, E.M. Schmelz, A.H. Merrill Jr, J. Nutr. 124 (1994) 615–620. doi: 10.1093/jn/124.5.615
21. [21]
  E.M. Schmelz, D.L. Dillehay, S.K. Webb, et al., Cancer Res. 56 (1996) 4936–4941.
22. [22]
  H. Symolon, E.M. Schmelz, D.L. Dillehay, A.H. Merrill Jr, J. Nutr. 134 (2004) 1157–1161. doi: 10.1093/jn/134.5.1157
23. [23]
  L.A. Lemonnier, D.L. Dillehay, M.J. Vespremi, et al., Arch. Biochem. Biophys. 419 (2003) 129–138. doi: 10.1016/j.abb.2003.08.023
24. [24]
  J.C. Mazzei, H. Zhou, B.P. Brayfield, et al., J. Nutr. Biochem. 22 (2011) 1160–1171. doi: 10.1016/j.jnutbio.2010.09.017
1. [1]
  Peisi Xie , Jing Chen , Yongjun Xia , Zongwei Cai . MALDI and MALDI-2 mass spectrometry imaging contribute to revealing the alternations in lipid metabolism in germinating soybean seeds. Chinese Chemical Letters, 2025, 36(8): 110595-. doi: 10.1016/j.cclet.2024.110595
2. [2]
  Bohan Chen , Liming Gong , Jing Feng , Mingji Jin , Liqing Chen , Zhonggao Gao , Wei Huang . Research advances of nanoparticles for CAR-T therapy in solid tumors. Chinese Chemical Letters, 2024, 35(9): 109432-. doi: 10.1016/j.cclet.2023.109432
3. [3]
  Zhihong LUO , Yan SHI , Jinyu AN , Deyi ZHENG , Long LI , Quansheng OUYANG , Bin SHI , Jiaojing SHAO . Two-dimensional silica-modified polyethylene oxide solid polymer electrolyte to enhance the performance of lithium-ion batteries. Chinese Journal of Inorganic Chemistry, 2024, 40(5): 1005-1014. doi: 10.11862/CJIC.20230444
4. [4]
  Jing Guo , Jianzhong Ma , Junli Liu , Guanjie Huang , Xiaoting Zhou , Francesco Parrino , Riccardo Ceccato , Leonardo Palmisano , Boon-Junn Ng , Lutfi Kurnianditia Putri , Huaxing Li , Rongjie Li , Gang Liu , Yang Wang , Nikolay Kornienko , Shan-Shan Zhu , Zhenwei Zhang , Xiaoming Liu , Nur Atika Nikma Dahlan , Siang-Piao Chai , Jianmin Ma . Two-dimensional nanomaterials for environmental catalysis roadmap towards 2030. Chinese Chemical Letters, 2025, 36(9): 110988-. doi: 10.1016/j.cclet.2025.110988
5. [5]
  Changxing Yang , Guxia Wang , Shengwei Guo , Jianlin Sun . Potential and progress of two-dimensional nanomaterials in oil-based lubrication. Chinese Chemical Letters, 2025, 36(9): 111178-. doi: 10.1016/j.cclet.2025.111178
6. [6]
  Zhilei Zhang , Yanan Sun , Xiaosong Shi , Xiaozhe Yin , Dawei Liu , Erjing Wang , Jie Liu , Yuanyuan Hu , Lang Jiang . Molecular tailoring towards two-dimensional organic crystals at the thickness limit. Chinese Chemical Letters, 2025, 36(9): 110786-. doi: 10.1016/j.cclet.2024.110786
7. [7]
  Yang LU , Liangliang HUANG , Wei ZHAO , Xin WANG , Yanfeng BI . Syntheses, proton conduction, and transport mechanism of two three-dimensional lanthanum phosphite-oxalates. Chinese Journal of Inorganic Chemistry, 2025, 41(10): 2127-2137. doi: 10.11862/CJIC.20250149
8. [8]
  Yuhang Li , Yang Ling , Yanhang Ma . Application of three-dimensional electron diffraction in structure determination of zeolites. Chinese Journal of Structural Chemistry, 2024, 43(4): 100237-100237. doi: 10.1016/j.cjsc.2024.100237
9. [9]
  Zhenzhu Wang , Chenglong Liu , Yunpeng Ge , Wencan Li , Chenyang Zhang , Bing Yang , Shizhong Mao , Zeyuan Dong . Differentiated self-assembly through orthogonal noncovalent interactions towards the synthesis of two-dimensional woven supramolecular polymers. Chinese Chemical Letters, 2024, 35(5): 109127-. doi: 10.1016/j.cclet.2023.109127
10. [10]
  Xin-Tong Zhao , Jin-Zhi Guo , Wen-Liang Li , Jing-Ping Zhang , Xing-Long Wu . Two-dimensional conjugated coordination polymer monolayer as anode material for lithium-ion batteries: A DFT study. Chinese Chemical Letters, 2024, 35(6): 108715-. doi: 10.1016/j.cclet.2023.108715
11. [11]
  Tian Yang , Yi Liu , Lina Hua , Yaoyao Chen , Wuqian Guo , Haojie Xu , Xi Zeng , Changhao Gao , Wenjing Li , Junhua Luo , Zhihua Sun . Lead-free hybrid two-dimensional double perovskite with switchable dielectric phase transition. Chinese Chemical Letters, 2024, 35(6): 108707-. doi: 10.1016/j.cclet.2023.108707
12. [12]
  Zhuoer Cai , Yinan Zhang , Xiu-Ni Hua , Baiwang Sun . Phase transition arising from order-disorder motion in stable layered two-dimensional perovskite. Chinese Journal of Structural Chemistry, 2024, 43(11): 100426-100426. doi: 10.1016/j.cjsc.2024.100426
13. [13]
  Jiahao Li , Guinan Chen , Chunhong Chen , Yuanyuan Lou , Zhihao Xing , Tao Zhang , Chengtao Gong , Yongwu Peng . Modulated synthesis of stoichiometric and sub-stoichiometric two-dimensional covalent organic frameworks for enhanced ethylene purification. Chinese Chemical Letters, 2025, 36(1): 109760-. doi: 10.1016/j.cclet.2024.109760
14. [14]
  Muhammad Riaz , Rakesh Kumar Gupta , Di Sun , Mohammad Azam , Ping Cui . Selective adsorption of organic dyes and iodine by a two-dimensional cobalt(II) metal-organic framework. Chinese Journal of Structural Chemistry, 2024, 43(12): 100427-100427. doi: 10.1016/j.cjsc.2024.100427
15. [15]
  Xi Zhou , Shengyao Wang . Dynamic two-dimensional covalent organic frameworks via ‘wine rack' design. Chinese Journal of Structural Chemistry, 2025, 44(4): 100464-100464. doi: 10.1016/j.cjsc.2024.100464
16. [16]
  Jiayu Zeng , Minhui Liu , Ting Yang , Jia Huang , Songjiao Li , Wanting Zhang , Dan Cheng , Longwei He , Jia Zhou . Two-dimensional design strategy to construct smart dual-responsive fluorescent probe for the precise tracking of ischemic stroke. Chinese Chemical Letters, 2025, 36(5): 110166-. doi: 10.1016/j.cclet.2024.110166
17. [17]
  Xiaoli CHEN , Zhihong LUO , Yuzhu XIONG , Aihua WANG , Xue CHEN , Jiaojing SHAO . Inhibitory effect of the interlayer of two-dimensional vermiculite on the polysulfide shuttle in lithium-sulfur batteries. Chinese Journal of Inorganic Chemistry, 2025, 41(8): 1661-1671. doi: 10.11862/CJIC.20250075
18. [18]
  Chao Ma , Peng Guo , Zhongmin Liu . DNL-16: A new zeolitic layered silicate unraveled by three-dimensional electron diffraction. Chinese Journal of Structural Chemistry, 2024, 43(4): 100235-100235. doi: 10.1016/j.cjsc.2024.100235
19. [19]
  Shiyu Hou , Maolin Sun , Liming Cao , Chaoming Liang , Jiaxin Yang , Xinggui Zhou , Jinxing Ye , Ruihua Cheng . Computational fluid dynamics simulation and experimental study on mixing performance of a three-dimensional circular cyclone-type microreactor. Chinese Chemical Letters, 2024, 35(4): 108761-. doi: 10.1016/j.cclet.2023.108761
20. [20]
  Runtan Gao , Yang Zong , Tingting Li , Na Liu , Zongquan Wu . Three-dimensional supramolecular polymer frameworks with precisely tunable and large apertures for enzyme encapsulation. Chinese Chemical Letters, 2026, 37(1): 111582-. doi: 10.1016/j.cclet.2025.111582

Get Citation

PDF

XML

Metrics

PDF Downloads(7)
Abstract views(1700)
HTML views(267)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142