Comparative Proteomic Analysis of the Mitochondria of Menstrual Stem Cells and Ovarian Cancer Cells

Overview

Journal Exp Ther Med

Specialty Pathology

Date 2023 Feb 10

PMID 36761005

Authors

Xiuhui Chen

Wen Zhong

Yue Chang

Tiefang Song

Botong Liu

Xianchao Kong

Qingfei Kong

Affiliations

Soon will be listed here.

Abstract

Mitochondrial transplantation is a popular field of research in cell-free therapy. Menstrual stem cells (MenSCs) are potential donor cells for provision of foreign mitochondria. The present study aimed to investigate the potential effects of MenSC-derived mitochondria on ovarian cancer from the perspective of protein expression profiling. MenSCs were harvested from menstrual blood. The mitochondria were isolated from MenSCs and ovarian cancer cell line SKOV3. A label-free mitochondria proteomics and analysis were performed by comparing the protein expression in mitochondria of MenSCs and SKOV3 cells. The differentially expressed proteins with fold-change >2 were analyzed by Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway and protein domain enrichment, protein interaction networks and parallel reaction monitoring (PRM) analysis. In total, 592 proteins that were found to have increased expression in the mitochondria of MenSCs were analyzed. Functional enrichment analysis revealed these proteins were enriched in metabolism-associated pathway entries including 'oxidative phosphorylation' (OXPHOS) pathway. PRM analysis confirmed that four of 6 candidate proteins in the OXPHOS pathway showed similar increasing trends. The protein domain enrichment analysis showed that domains such as 'thioredoxin domain' were significantly enriched. Based on these findings, it was hypothesized that mitochondria from MenSCs have the potential to enhance progression of ovarian cancer likely mediated by the enrichment of OXPHOS-associated metabolic pathways.

References

Warburg O, Wind F, Negelein E . THE METABOLISM OF TUMORS IN THE BODY. J Gen Physiol. 2009; 8(6):519-30. PMC: 2140820. DOI: 10.1085/jgp.8.6.519. View

Pustylnikov S, Costabile F, Beghi S, Facciabene A . Targeting mitochondria in cancer: current concepts and immunotherapy approaches. Transl Res. 2018; 202:35-51. PMC: 6456045. DOI: 10.1016/j.trsl.2018.07.013. View

Caicedo A, Fritz V, Brondello J, Ayala M, Dennemont I, Abdellaoui N . MitoCeption as a new tool to assess the effects of mesenchymal stem/stromal cell mitochondria on cancer cell metabolism and function. Sci Rep. 2015; 5:9073. PMC: 4358056. DOI: 10.1038/srep09073. View

Foo J, Looi Q, Chong P, Hassan N, Yeo G, Ng C . Comparing the Therapeutic Potential of Stem Cells and their Secretory Products in Regenerative Medicine. Stem Cells Int. 2021; 2021:2616807. PMC: 8378970. DOI: 10.1155/2021/2616807. View

Gomzikova M, James V, Rizvanov A . Mitochondria Donation by Mesenchymal Stem Cells: Current Understanding and Mitochondria Transplantation Strategies. Front Cell Dev Biol. 2021; 9:653322. PMC: 8058353. DOI: 10.3389/fcell.2021.653322. View

Ke X, Li L, Li J, Zheng M, Liu P . Anti-oncogenic PTEN induces ovarian cancer cell senescence by targeting P21. Cell Biol Int. 2021; 46(1):118-128. PMC: 9298057. DOI: 10.1002/cbin.11709. View

Vaupel P, Schmidberger H, Mayer A . The Warburg effect: essential part of metabolic reprogramming and central contributor to cancer progression. Int J Radiat Biol. 2019; 95(7):912-919. DOI: 10.1080/09553002.2019.1589653. View

Pavlova N, Thompson C . The Emerging Hallmarks of Cancer Metabolism. Cell Metab. 2016; 23(1):27-47. PMC: 4715268. DOI: 10.1016/j.cmet.2015.12.006. View

Xu H, Chen L, Zhou S, Li Y, Xiang C . Multifunctional role of microRNAs in mesenchymal stem cell-derived exosomes in treatment of diseases. World J Stem Cells. 2020; 12(11):1276-1294. PMC: 7705472. DOI: 10.4252/wjsc.v12.i11.1276. View

10.

Emmings E, Mullany S, Chang Z, Landen Jr C, Linder S, Bazzaro M . Targeting Mitochondria for Treatment of Chemoresistant Ovarian Cancer. Int J Mol Sci. 2019; 20(1). PMC: 6337358. DOI: 10.3390/ijms20010229. View

11.

Heil L, Remes P, MacCoss M . Comparison of Unit Resolution Versus High-Resolution Accurate Mass for Parallel Reaction Monitoring. J Proteome Res. 2021; 20(9):4435-4442. DOI: 10.1021/acs.jproteome.1c00377. View

12.

Chen L, Qu J, Xiang C . The multi-functional roles of menstrual blood-derived stem cells in regenerative medicine. Stem Cell Res Ther. 2019; 10(1):1. PMC: 6318883. DOI: 10.1186/s13287-018-1105-9. View

13.

Nakamura Y, Park J, Hayakawa K . Therapeutic use of extracellular mitochondria in CNS injury and disease. Exp Neurol. 2019; 324:113114. PMC: 6980730. DOI: 10.1016/j.expneurol.2019.113114. View

14.

Raik S, Kumar A, Bhattacharyya S . Insights into cell-free therapeutic approach: Role of stem cell "soup-ernatant". Biotechnol Appl Biochem. 2017; 65(2):104-118. DOI: 10.1002/bab.1561. View

15.

Chen L, Qu J, Cheng T, Chen X, Xiang C . Menstrual blood-derived stem cells: toward therapeutic mechanisms, novel strategies, and future perspectives in the treatment of diseases. Stem Cell Res Ther. 2019; 10(1):406. PMC: 6925480. DOI: 10.1186/s13287-019-1503-7. View

16.

Liu K, Zhou Z, Pan M, Zhang L . Stem cell-derived mitochondria transplantation: A promising therapy for mitochondrial encephalomyopathy. CNS Neurosci Ther. 2021; 27(7):733-742. PMC: 8193690. DOI: 10.1111/cns.13618. View

17.

Lin H, Zhang W, Xu Y, You Z, Zheng M, Liu Z . 4D label-free quantitative proteomics analysis to screen potential drug targets of Jiangu Granules treatment for postmenopausal osteoporotic rats. Front Pharmacol. 2022; 13:1052922. PMC: 9663813. DOI: 10.3389/fphar.2022.1052922. View

18.

Karlenius T, Tonissen K . Thioredoxin and Cancer: A Role for Thioredoxin in all States of Tumor Oxygenation. Cancers (Basel). 2013; 2(2):209-32. PMC: 3835076. DOI: 10.3390/cancers2020209. View

19.

Wang J, Li H, Yao Y, Zhao T, Chen Y, Shen Y . Stem cell-derived mitochondria transplantation: a novel strategy and the challenges for the treatment of tissue injury. Stem Cell Res Ther. 2018; 9(1):106. PMC: 5899391. DOI: 10.1186/s13287-018-0832-2. View

20.

Matassa D, Amoroso M, Lu H, Avolio R, Arzeni D, Procaccini C . Oxidative metabolism drives inflammation-induced platinum resistance in human ovarian cancer. Cell Death Differ. 2016; 23(9):1542-54. PMC: 5072430. DOI: 10.1038/cdd.2016.39. View