Metabolomics profiling reveals differences in proliferation between tumorigenic and non-tumorigenic Madin-Darby canine kidney (MDCK) cells

Na Sun; Yuchuan Zhang; Jian Dong; Geng Liu; Zhenbin Liu; Jiamin Wang; Zilin Qiao; Jiayou Zhang; Kai Duan; Xuanxuan Nian; Zhongren Ma; Xiaoming Yang

doi:10.7717/peerj.16077

Metabolomics profiling reveals differences in proliferation between tumorigenic and non-tumorigenic Madin-Darby canine kidney (MDCK) cells

PeerJ. 2023 Sep 20:11:e16077. doi: 10.7717/peerj.16077. eCollection 2023.

Authors

Na Sun^#^{1

2}, Yuchuan Zhang^#¹, Jian Dong¹, Geng Liu¹, Zhenbin Liu^{1

2}, Jiamin Wang^{1

2

3}, Zilin Qiao^{1

2

3}, Jiayou Zhang^{4

5}, Kai Duan^{4

5}, Xuanxuan Nian^{4

5}, Zhongren Ma^{1

2

6}, Xiaoming Yang^{5

7}

Affiliations

¹ Gansu Technology Innovation Center of Animal Cell, Biomedical Research Center, Northwest Minzu University, Lanzhou, China.
² Engineering Research Center of Key Technology and Industrialization of Cell-based Vaccine, Ministry of Education, Lanzhou, China.
³ Gansu Provincial Bioengineering Materials Engineering Research Center, Lanzhou, China.
⁴ Wuhan Institute of Biological Products Co., Ltd., Wuhan, China.
⁵ National Engineering Technology Research Center for Combined Vaccines, Wuhan, China.
⁶ Key Laboratory of Biotechnology and Bioengineering of National Ethnic Affairs Commission, Biomedical Research Center, Northwest Minzu University, Lanzhou, China.
⁷ China National Biotech Group Company Limited, Beijing, China.

^# Contributed equally.

Abstract

Background: Madin-Darby canine kidney (MDCK) cells are a cellular matrix in the production of influenza vaccines. The proliferation rate of MDCK cells is one of the critical factors that determine the vaccine production cycle. It is yet to be determined if there is a correlation between cell proliferation and alterations in metabolic levels. This study aimed to explore the metabolic differences between MDCK cells with varying proliferative capabilities through the use of both untargeted and targeted metabolomics.

Methods: To investigate the metabolic discrepancies between adherent cell groups (MDCK-M60 and MDCK-CL23) and suspension cell groups (MDCK-XF04 and MDCK-XF06), untargeted and targeted metabolomics were used. Utilizing RT-qPCR analysis, the mRNA expressions of key metabolites enzymes were identified.

Results: An untargeted metabolomics study demonstrated the presence of 81 metabolites between MDCK-M60 and MDCK-CL23 cells, which were mainly affected by six pathways. An analysis of MDCK-XF04 and MDCK-XF06 cells revealed a total of 113 potential metabolites, the majority of which were impacted by ten pathways. Targeted metabolomics revealed a decrease in the levels of choline, tryptophan, and tyrosine in MDCK-CL23 cells, which was in accordance with the results of untargeted metabolomics. Additionally, MDCK-XF06 cells experienced a decrease in 5'-methylthioadenosine and tryptophan, while S-adenosylhomocysteine, kynurenine, 11Z-eicosenoic acid, 3-phosphoglycerate, glucose 6-phosphate, and phosphoenolpyruvic acid concentrations were increased. The mRNA levels of MAT1A, MAT2B, IDO1, and IDO2 in the two cell groups were all increased, suggesting that S-adenosylmethionine and tryptophan may have a significant role in cell metabolism.

Conclusions: This research examines the effect of metabolite fluctuations on cell proliferation, thus offering a potential way to improve the rate of MDCK cell growth.

Keywords: Cell proliferation; Choline metabolism; IDO; MAT; MDCK cells; S-adenosylmethionine; Targeted metabolomics; Tryptophan metabolism; Untargeted metabolomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carcinogenesis
Cell Proliferation
Dogs
Kidney
Madin Darby Canine Kidney Cells
Metabolomics*
Tryptophan*

Substances

Tryptophan
5'-methylthioadenosine

Grants and funding

This research was funded by scientific research project for talents introduced by Northwest Minzu University, grant number xbmuyjrc2020022; the National Natural Science Foundation of China, grant number 32160164; Primary Research & Development Plan of Gansu Province, grant number 21YF1FA222 and 21JR1RA209. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.