Skip to main content
SpringerLink
Log in

Effect of IGFBP6 Knockdown on Proteins Regulating Exosome Synthesis and Secretion in MDA-MB-231 Cell Line

  • Published:
Bulletin of Experimental Biology and Medicine Aims and scope

One of the potential causes of cancer recurrence is disruption of the cell—cell communication in the primary tumors that is realized, among other things, through secretion and uptake of exosomes by cells. Low expression of the IGFBP6 gene (insulin-like growth factor binding protein 6) is associated with a high recurrence rate and can serve as a prognostic marker of luminal breast cancer. The knockdown of the IGFBP6 gene leads to significant changes in lipid metabolism. We performed a quantitative analysis of both exosomes and proteins involved in the mechanism of their biogenesis. Changes in the expression profile of mRNAs and their proteins responsible for the synthesis and secretion of exosomes were revealed. We showed a decrease in the expression of the of the VPS28 gene mRNA (vacuolar protein sorting-associated protein 28) and the corresponding protein by 2.3 and 5.6 times, respectively. The secretion of exosomes by MDA-MB-231 cells with IGFBP6 knockdown decreased by 2 times. We discussed a mechanism of disruption of cell—cell communication.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Nikulin S, Zakharova G, Poloznikov A, Raigorodskaya M, Wicklein D, Schumacher U, Nersisyan S, Bergquist J, Bakalkin G, Astakhova L, Tonevitsky A. Effect of the expression of ELOVL5 and IGFBP6 genes on the metastatic potential of breast cancer cells. Front. Genet. 2021;12:662843. https://doi.org/10.3389/fgene.2021.662843

  2. Song F, Zhou X.X, Hu Y, Li G, Wang Y. The roles of Insulin-Like Growth Factor binding protein family in development and diseases. Adv. Ther. 2021;38(2):885-903. https://doi.org/10.1007/s12325-020-01581-x

    Article  CAS  PubMed  Google Scholar 

  3. Bach LA, Fu P, Yang Z. Insulin-like growth factor-binding protein-6 and cancer. Clin. Sci. (Lond). 2013;124(4):215-229. https://doi.org/10.1042/CS20120343

    Article  CAS  PubMed  Google Scholar 

  4. Turchinovich A, Tonevitsky AG, Cho WC, Burwinkel B. Check and mate to exosomal extracellular miRNA: new lesson from a new approach. Front. Mol. Biosci. 2015;2:11. https://doi.org/10.3389/fmolb.2015.00011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Palazzolo G, Albanese NN, DI Cara G, Gygax D, Vittorelli ML, Pucci-Minafra I. Proteomic analysis of exosome-like vesicles derived from breast cancer cells. Anticancer Res. 2012;32(3):847-860.

    CAS  PubMed  Google Scholar 

  6. Melo SA, Sugimoto H, O’Connell JT, Kato N, Villanueva A, Vidal A, Qiu L, Vitkin E, Perelman LT, Melo CA, Lucci A, Ivan C, Calin GA, Kalluri R. Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis. Cancer Cell. 2014;26(5):707-721. https://doi.org/10.1016/j.ccell.2014.09.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Meldolesi J. Exosomes and ectosomes in intercellular communication. Curr. Biol. 2018;28(8):R435-R444. https://doi.org/10.1016/j.cub.2018.01.059

    Article  CAS  PubMed  Google Scholar 

  8. Kent WJ, Sugnet CW, Furey TS, Roskin KM, Pringle TH, Zahler AM, Haussler D. The human genome browser at UCSC. Genome Res. 2002;12(6):996-1006. https://doi.org/10.1101/gr.229102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ye J, Coulouris G, Zaretskaya I, Cutcutache I, Rozen S, Madden TL. Primer-BLAST: a tool to design target-specific primers for polymerase chain reaction. BMC Bioinformatics. 2012;13:134. https://doi.org/10.1186/1471-2105-13-134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Owczarzy R, Tataurov AV, Wu Y, Manthey JA, McQuisten KA, Almabrazi HG, Pedersen KF, Lin Y, Garretson J, McEntaggart NO, Sailor CA, Dawson RB, Peek AS. IDT SciTools: a suite for analysis and design of nucleic acid oligomers. Nucleic Acids Res. 2008;36(Web Server issue):W163-9. https://doi.org/10.1093/nar/gkn198

  11. Maltseva DV, Khaustova NA, Fedotov NN, Matveeva EO, Lebedev AE, Shkurnikov MU, Galatenko VV, Schumacher U, Tonevitsky AG. High-throughput identification of reference genes for research and clinical RT-qPCR analysis of breast cancer samples. J. Clin. Bioinforma. 2013;3(1):13. https://doi.org/10.1186/2043-9113-3-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Miyanishi M, Tada K, Koike M, Uchiyama Y, Kitamura T, Nagata S. Identification of Tim4 as a phosphatidylserine receptor. Nature. 2007;450:435-439. https://doi.org/10.1038/nature06307

    Article  CAS  PubMed  Google Scholar 

  13. Muller L, Hong CS, Stolz DB, Watkins SC, Whiteside TL. Isolation of biologically-active exosomes from human plasma. J. Immunol. Methods. 2014;411:55-65. https://doi.org/10.1016/j.jim.2014.06.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Wu Y, Deng W, Klinke DJ 2nd. Exosomes: improved methods to characterize their morphology, RNA content, and surface protein biomarkers. Analyst. 2015;140(19):6631-6642. https://doi.org/10.1039/c5an00688k

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Williams RL, Urbé S. The emerging shape of the ESCRT machinery. Nat. Rev. Mol. Cell Biol. 2007;8(5):355-368. https://doi.org/10.1038/nrm2162

    Article  CAS  PubMed  Google Scholar 

  16. Hessvik NP, Llorente A. Current knowledge on exosome biogenesis and release. Cell. Mol. Life Sci. 2018;75(2):193-208. https://doi.org/10.1007/s00018-017-2595-9

    Article  CAS  PubMed  Google Scholar 

  17. Malhi H. Emerging role of extracellular vesicles in liver diseases. Am. J. Physiol. Gastrointest. Liver Physiol. 2019;317(5):G739-G749. https://doi.org/10.1152/ajpgi.00183.2019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Spencer N, Yeruva L. Role of bacterial infections in extracellular vesicles release and impact on immune response. Biomed. J. 2021;44(2):157-164. https://doi.org/10.1016/j.bj.2020.05.006

    Article  CAS  PubMed  Google Scholar 

  19. Phuyal S, Hessvik NP, Skotland T, Sandvig K, Llorente A. Regulation of exosome release by glycosphingolipids and flotillins. FEBS J. 2014;281(9):2214-2227. https://doi.org/10.1111/febs.12775

    Article  CAS  PubMed  Google Scholar 

  20. Villarroya-Beltri C, Baixauli F, Gutiérrez-Vázquez C, Sánchez-Madrid F, Mittelbrunn M. Sorting it out: regulation of exosome loading. Semin. Cancer Biol. 2014;28:3-13. https://doi.org/10.1016/j.semcancer.2014.04.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Bobrie A, Colombo M, Raposo G, Théry C. Exosome secretion: molecular mechanisms and roles in immune responses. Traffic. 2011;12(12):1659-1668. https://doi.org/10.1111/j.1600-0854.2011.01225.x

    Article  CAS  PubMed  Google Scholar 

  22. Huang J, Xiong J, Yang L, Zhang J, Sun S, Liang Y. Cell-free exosome-laden scaffolds for tissue repair. Nanoscale. 2021;13(19): 8740-8750. https://doi.org/10.1039/d1nr01314a

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Faculty of Biology and Biotechnologies, National Research University Higher School of Economics, Moscow, Russia

    A. S. Efimova, I. D. Antipenko, P. V. Balan & S. A. Tonevitskaya

  2. Faculty of Biology, M. V. Lomonosov Moscow State University, Moscow, Russia

    E. A. Evtushenko

Authors
  1. A. S. Efimova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. D. Antipenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. A. Evtushenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. V. Balan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. A. Tonevitskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. S. Efimova.

Additional information

Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 1, pp. 47-51, March, 2023

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Efimova, A.S., Antipenko, I.D., Evtushenko, E.A. et al. Effect of IGFBP6 Knockdown on Proteins Regulating Exosome Synthesis and Secretion in MDA-MB-231 Cell Line. Bull Exp Biol Med 175, 157–161 (2023). https://doi.org/10.1007/s10517-023-05828-9

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10517-023-05828-9

Keywords

Search

Navigation