Polymers of 2,5-Dihydroxybenzoic Acid Induce Formation of Spheroids in Mammalian Cells

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

Cells attached to a substrate and grown in two dimensions (2D) or suspended culture cannot accurately replicate intercellular interactions in tissues and organs. Spheroids, being three-dimensional (3D) formations, are more accurately reproduce the structure of organs or neoplasms. Spheroids compared to 2D cultures demonstrate an increased survival, corresponding morphology, and a hypoxic core, which is observed in native tumors in vivo. Tumor cell spheroids also represent models of the metastatic process. Therefore, spheroids are currently widely used for testing new anticancer drugs. However, obtaining and using 3D cultures can be associated with a number of difficulties, such as the need for expensive reagents and equipment, the low rate of formation of spheroids of the required size, and the occurrence of long-term changes in cell metabolism, which depend on the methods used to create spheroids. We have found that incubation of tumor and normal cells in the presence of polymers of 2,5-dihydroxybenzoic acid (2,5-DHBA) that are nontoxic to cells can induce the formation of 3D structures. Based on this, a new method for the rapid production of 3D cultures is developed and this approach does not require the use of additional equipment, expensive reagents, and does not have a long-term effect on cell homeostasis. The spheroids obtained by this method represent models of three-dimensional structures and can be used for biological studies of intercellular interactions and detection of pharmaceutical products.

About the authors

G. K. Rystsov

Federal Research Center “Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences”,
Scriabin Institute of Biochemistry and Physiology of Microorganisms RAS

Author for correspondence.
Email: gleb.8.ristsoff@gmail.com
Russia, 142290, Pushchino, prosp. Nauki 5

A. V. Lisov

Federal Research Center “Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences”,
Scriabin Institute of Biochemistry and Physiology of Microorganisms RAS

Email: gleb.8.ristsoff@gmail.com
Russia, 142290, Pushchino, prosp. Nauki 5

M. Yu. Zemskova

Federal Research Center “Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences”,
Scriabin Institute of Biochemistry and Physiology of Microorganisms RAS

Author for correspondence.
Email: gleb.8.ristsoff@gmail.com
Russia, 142290, Pushchino, prosp. Nauki 5

References

  1. Egeblad M., Nakazone E.S., Werb Z. // Dev. Cell. 2010. V. 18. P. 884–901. https://doi.org/10.1016/j.devcel.2010.05.012
  2. Mulholland T., McAllister M., Patek S., Flint D., Underwood M., Sim A., Edwards J., Zagnoni M. // Sci. Rep. 2018. V. 8. P. 14672. https://doi.org/10.1038/s41598-018-33055-0
  3. Lin R.Z., Chang H.Y. // Biotechnol. J. 2008. V. 3. P. 1172–1184. https://doi.org/10.1002/biot.200700228
  4. Harrison R.G., Greenman M.J., Mall P., Jackson C.M. // Anat. Rec. 1907. V. 1. P. 116–128. https://doi.org/10.1002/ar.1092340113
  5. Breslin S., O’Driscoll L. // Drug Dis. Today. 2013. V. 18. P. 240–249. https://doi.org/10.1016/j.drudis.2012.10.003
  6. Desoize B., Jardillier J. // Crit. Rev. Oncol. Hematol. 2000. V. 36. P. 193–207.
  7. Dardousis K., Voolstra C., Roengvoraphoj M., Sekandarzad A., Mesghenna S., Winkler J., Ko Y., Hescheler J., Sachinidis A. // Mol. Ther. 2007. V. 15. P. 94–102. https://doi.org/10.1038/sj.mt.6300003
  8. Ghosh S., Joshi M.B., Ivanov D., Feder-Mengus C., Spagnoli G.C., Martin I., Erne P., Resink T.J. // FEBS Lett. 2007. V. 581. P. 4523–4528. https://doi.org/10.1016/j.febslet.2007.08.038
  9. Feder-Mengus C., Ghosh S., Weber W.P., Wyler S., Zajac P., Terracciano L., Oertli D., Heberer M., Martin I., Spagnoli G., Reschner A. // Br. J. Cancer. 2007. V. 96. P. 1072–1082. https://doi.org/10.1038/sj.bjc.6603664
  10. Durand R.E. // Cancer Chemother. Pharmacol. 1990. V. 26. P. 198–204. https://doi.org/10.1007/bf02897199
  11. Bartholoma P., Reininger-Mack I.A., Zhang Z., Thielecke H., Robitzki A. // J. Biomol. Screen. 2005. V. 10. P. 705–714. https://doi.org/10.1177/1087057105277841
  12. Friedrich J., Seidel C., Ebner R., Kunz-Schughart L.A. // Nature Protoc. 2009. V. 4. P. 309–324. https://doi.org/10.1038/nprot.2008.226
  13. Kunz-Schughart L.A., Freyer J.P., Hofstaedter F., Ebner R. // J. Biomol. Screen. 2004. V. 9. P. 273–285. https://doi.org/10.1177/1087057104265040
  14. Dubessy C., Merlin J.M., Marchal C., Guillemin F. // Crit. Rev. Oncol. Hematol. 2000. V. 36. P. 179–192. https://doi.org/10.1016/s1040-8428(00)00085-8
  15. Lin R.Z., Chu W.C., Chiang C.C., Lai C.H., Chang H.Y. // Tissue Eng. Part. C Methods. 2008. V. 14. P. 197–205. https://doi.org/10.1089/ten.tec.2008.0061
  16. Steer D.L., Nigam S.K. // Am. J. Physiol. Renal. Physiol. 2004. V. 1. P. 1–7.
  17. Ivascu A., Kubbies M. // J. Biomol. Screen. 2006. V. 11. P. 922–932. https://doi.org/10.1177/1087057106292763
  18. Friedrich J., Seidel C., Ebner R., Kunz-Schughart L.A. // Nat. Protoc. 2009. V. 4. P. 309–324. https://doi.org/10.1038/nprot.2008.226
  19. Klinder A., Markhoff J., Jonitz-Heincke A., Sterna P., Salamon A., Bader R. // Exp. Ther. Med. 2019. V. 17. P. 2004–2012. https://doi.org/10.3892/etm.2019.7204
  20. Keller G.M. // Curr. Opin. Cell Biol. 1995. V. 7. P. 862–869. https://doi.org/10.1016/0955-0674(95)80071-9
  21. Kelm J.M., Timmins N.E., Brown C.J., Fussenegger M., Nielsen L.K. // Biotechnol. Bioeng. 2003. V. 83. P. 173–180. https://doi.org/10.1002/bit.10655
  22. Kurosawa H. // J. Biosci. Bioeng. 2007. V. 3. P. 389–398. https://doi.org/10.1263/jbb.103.389
  23. Timmins N.E., Nielsen L.K. // Methods Mol. Med. 2007. V. 140. P. 141–151. https://doi.org/10.1007/978-1-59745-443-8_8
  24. Kim J.B. // Semin. Cancer Biol. 2005. V. 5. P. 365–377. https://doi.org/10.1016/j.semcancer.2005.05.002
  25. Barrila J., Radtke A.L., Crabbé A., Sarker S.F., Herbst-Kralovetz M.M., Ott C.M., Nickerson C.A. // Nat. Rev. Microbiol. 2010. V. 8. P. 791–801. https://doi.org/10.1038/nrmicro2423
  26. Lin R.Z., Chang H.Y. // Biotechnol. J. 2008. V. 3. P. 1172–1184. https://doi.org/10.1002/biot.200700228
  27. Lü W.D., Zhang L., Wu C.L., Liu Z.G., Lei G.Y., Liu J., Gao W., Hu Y.R. // PLoS One. 2014. V. 9. P. e103672. https://doi.org/10.1371/journal.pone.0103672
  28. Hughes C.S., Postovit L.M., Lajoie G.A. // Proteomics. 2010. V. 10. P. 1886–1890. https://doi.org/10.1002/pmic.200900758
  29. Porzionato A., Stocco E., Barbon S., Grandi F., Macchi V., De Caro R. // Int. J. Mol. Sci. 2018. V. 19. P. 4117. https://doi.org/10.3390/ijms19124117
  30. Nath S., Devi G.R. // Pharmacol. Ther. 2016. V. 163. P. 94–108. https://doi.org/10.1016/j.pharmthera.2016.03.013
  31. Sodunke T.R., Turner K.K., Caldwell S.A., McBride K.W., Reginato M.J., Noh H.M. // Biomaterials. 2007. V. 28. P. 4006–4016.
  32. Zaki M.Y.W., Shetty S., Wilkinson A.L., Patten D.A., Oakley F., Reeves H. // J. Vis. Exp. 2021. V. 175. P. e62868. https://doi.org/10.3791/62868
  33. Sourla A., Doillon C., Koutsilieris M. // Anticancer Res. 1996. V. 16. P. 2773–2780.
  34. Jiang T., Munguia-Lopez J.G., Flores-Torres S., Grant J., Vijayakumar S., De Leon-Rodriguez A., Kinsella M.J. // Sci. Rep. 2017. V. 7. P. 4575. https://doi.org/10.1038/s41598-017-04691-9
  35. Lisov A., Vrublevskaya V., Lisova Z., Leontievsky A., Morenkov O. // Viruses. 2015. V. 7. P. 5343–5360. https://doi.org/10.3390/v7102878
  36. Edmondson R., Broglie J.J., Adcock A.F., Yang L. // Assay Drug Dev. Technol. 2014. V. 12. P. 207–218. https://doi.org/10.1089/adt.2014.573
  37. Lin R.Z., Chang H.Y. // Biotechnol. J. 2008. V. 3. P. 1172–1184. https://doi.org/10.1002/biot.200700228
  38. Benien P., Swami A. // Future Oncol. 2014. V. 10. P. 1311–1327. https://doi.org/10.2217/fon.13.274
  39. Archibald M., Pritchard T., Nehoff H., Rosengren R.J., Greish K., Taurin S. // Int. J. Nanomed. 2016. V. 11. P. 179–200. https://doi.org/10.2147/IJN.S97286
  40. Roberts G.C., Morris P.G., Moss M.A., Maltby S.L., Palmer C.A., Nash C.E., Smart E., Holliday D.L., Speirs V. // PLoS One. 2016. V. 11. e0157004. https://doi.org/10.1371/journal.pone.0157004
  41. Takir G.G., Debelec-Butuner B., Korkmaz K.S. // Proceedings. 2018. V. 2. P. 1555. https://doi.org/10.3390/proceedings2251555
  42. Kim C.J., Terado T., Tambe Y., Mukaisho K., Sugihara H., Kawauchi A., Inoue H. // Int. J. Oncol. 2018. V. 52. P. 231–240. https://doi.org/10.3892/ijo.2017.4194
  43. Zhao L., Xiu J., Liu Y., Zhang T., Pan W., Zheng X., Zhang X. // Sci. Rep. 2019. V. 9. P. 19717. https://doi.org/10.1038/s41598-019-56241-0
  44. Froehlich K., Haeger J.D., Heger J., Pastuschek J., Photini S.M., Yan Y., Lupp A., Pfarrer C., Mrowka R., Schleußner E., Markert U.R., Schmidt A. // J. Mammary Gland Biol. Neoplasia. 2016. V. 21. P. 89–98. https://doi.org/10.1007/s10911-016-9359-2
  45. Rodríguez C.E., Reidel S.I., Bal de Kier Joffé E.D., Jasnis M.A., Fiszman G.L. // PLoS One. 2015. V. 10. P. e0137920. https://doi.org/10.1371/journal.pone.0137920
  46. Djordjevic B., Lange C.S. // Acta Oncol. 2006. V. 45. P. 412–420. https://doi.org/10.1080/02841860500520743
  47. Kim H., Phung Y., Ho M. // PLoS One. 2012. V. 7. e39556. https://doi.org/10.1371/journal.pone.0039556
  48. Betson M., Lozano E., Zhang J., Braga V.M. // J. Biol. Chem. 2002. V. 277. P. 36962–36969. https://doi.org/10.1074/jbc.m207358200
  49. Troitskaya O., Novak D., Nushtaeva A., Savinkova M., Varlamov M., Ermakov M., Richter V., Koval O. // Int. J. Mol. Sci. 2021. V. 22. P. 12937. https://doi.org/10.3390/ijms222312937
  50. Kitajima D., Kasamatsu A., Nakashima D., Miyamoto I., Kimura Y., Endo-Sakamoto Y., Shiiba M., Tanzawa H., Uzawa K. // Oncology Lett. 2018. V. 15. P. 7237–7242. https://doi.org/10.3892/ol.2018.8212
  51. Fukuhara S., Sako K., Noda K., Nagao K., Miura K., Mochizuki N. // Exp. Mol. Med. 2009. V. 41. P. 133–139. https://doi.org/10.3858/emm.2009.41.3.016
  52. Weinberg F., Han M.K.L, Dahmke I.N., Del Campo A., de Jonge N. // PLoS One. 2020. V. 15. P. e0234430. https://doi.org/10.1371/journal.pone.0234430
  53. Singh A., Winterbottom E., Daar I.O. // Front. Biosci. (Landmark Ed). 2012. V. 17. P. 473–497. https://doi.org/10.2741/3939
  54. Godoy-Parejo C., Deng C., Liu W., Chen G. // Stem. Cells. 2019. V. 37. P. 1030–1041. https://doi.org/10.1002/stem.3026
  55. Cockburn J.G., Richardson D.S., Gujral T.S., Mulligan L.M. // J. Clin. Endocrinol. Metab. 2010. V. 95. P. 342–346. https://doi.org/10.1210/jc.2010-0771
  56. Henry C., Hacker N., Ford C. // Oncotarget. 2017. V. 8. P. 112727–112738. https://doi.org/10.18632/oncotarget.22559
  57. Shin W.S., Park M.K., Lee Y.H., Kim K.W., Lee H., Lee S.T. // Cancer Sci. 2020. V. 111. P. 3292–3302. https://doi.org/10.1111/cas.14568
  58. Chiasson-MacKenzie C., McClatchey A.I. // Cold Spring. Harb. Perspect. Biol. 2018. V. 10. P. a029215. https://doi.org/10.1101/cshperspect.a029215
  59. Kim Y.B., Nikoulina S.E., Ciaraldi T.P., Henry R.R., Kahn B.B. // J. Clin. Invest. 1999. V. 104. P. 733–741. https://doi.org/10.1172/JCI6928
  60. Mackenzie R., Elliott B. // Diabetes Metab. Syndr. Obes. 2014. V. 7. P. 55–64. https://doi.org/10.2147/DMSO.S48260
  61. Li G., Ji X.D., Gao H., Zhao J.S., Xu J.F., Sun Z.J., Deng Y.Z., Shi S., Feng Y.X., Zhu Y.Q., Wang T., Li J.J., Xie D. // Nat. Commun. 2012. V. 3. P. 667. https://doi.org/10.1038/ncomms1675
  62. Akasov R., Gileva A., Zaytseva-Zotova D., Burov S., Chevalot I., Guedon E., Markvicheva E. // Biotechnol. Lett. 2017. V. 39. P. 45–53.
  63. Buckley C.D., Pilling D., Henriquez N.V., Parsonage G., Threlfall K., Scheel-Toellner D., Simmons D.L., Akbar A.N., Lord J.M., Salmon M. // Nature. 1999. V. 397. P. 534–539. https://doi.org/10.1038/17409
  64. Kang I.C., Kim D.S., Jang Y., Chung K.H. // Biochem. Bioph. Res. Comm. 2000. V. 275. P. 169–173. https://doi.org/10.1006/bbrc.2000.3130
  65. Ritchie C.K., Giordano A., Khalili K. // J. Cell Physiol. 2000. V. 184. P. 214–221. https://doi.org/10.1002/1097-4652(200008)184:2%3C214: :aid-jcp9%3E3.0.co;2-z
  66. Anuradh, C., Kanno S., Hirano S. // Cell Biol. Toxicol. 2000. V. 16. P. 275–283. https://doi.org/10.1023/a:1026758429238
  67. Рысцов Г.К., Лисов А.В., Земскова М.Ю. // Патент RU 2742689 C1, 2021.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2.

Download (64KB)
Indexing metadata
3.

Download (1MB)
Indexing metadata
4.

Download (1MB)
Indexing metadata
5.

Download (1MB)
Indexing metadata
6.

Download (412KB)
Indexing metadata
7.

Download (490KB)
Indexing metadata
8.

Download (158KB)
Indexing metadata

Copyright (c) 2022 Г.К. Рысцов, А.В. Лисов, М.Ю. Земскова