The effects of stem cell-conditioned media on malignancy behavior of breast cancer cells in vitro

Document Type : Original Articles

Authors

1 Department of Pathobiology, Faculty of Veterinary Medicine, University of Tabriz, 51665-1647, Tabriz, Iran

2 Immunology Research Center, Tabriz University of Medical Sciences, 51666-14761, Tabriz, Iran, and Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, 51666-14761, Tabriz, Iran

3 Immunology Research Center, Tabriz University of Medical Sciences, 51666-14761, Tabriz, Iran

4 Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, 51665-1647, Tabriz, Iran

10.32592/ARI.2024.79.6.1249

Abstract

Breast cancer is the most commonly diagnosed cancer among women worldwide. In recent years, there has been growing interest among researchers in exploring alternative therapeutic methods, including stem cell therapy. Therefore, this study aimed to investigate the effects of adipose-derived mesenchymal stem cell-conditioned media (AD-MSCs-CM) on apoptosis induction and migration inhibition of breast cancer cells (MDA-MB-231) in vitro. Here, malignant breast cancer cells (MDA-MB-231) and adipose mesenchymal stem cells (AD-MSC) were cultured separately in DMEM F12/FBS15% culture media in standard conditions. Subsequently, the conditioned media derived from AD-MSCs was exposed to the MDA-MB-231 cells. After 24 and 48 hours of exposure, the expression levels of CASP3, KRAS, and MMP9, were assessed using a qRT-PCR assay. Additionally, the proliferation and migration abilities of the cancer cells were evaluated using MTT and wound healing assays, respectively. Also, the protein expression of Caspase-3, K-RAS, and MMP-9 was examined using the western blot assay. Notably, the expression level of MMP9 and KRAS genes significantly decreased following AD-MSCs-CM treatment in MDA-MB-231 cells. Moreover, the expression level of CASP3 gene remarkably increased in the treated groups. Besides, the proliferation of MDA-MB-231 cells treated with AD-MSCs-CM was strongly reduced by MTT and wound healing assays. Furthermore, the AD-MSCs-CM demonstrated an increase in the activation of Caspase-3 and a decrease in the protein expressions of K-RAS and MMP-9. The findings of this study suggest that the AD-MSCs-CM have the potential to influence apoptosis, proliferation, and migration of breast cancer cells. Thus, it could be considered a promising therapeutic strategy for suppressing breast cancer. However, further testing and research are required to validate these findings and explore the full potential of this approach.

Keywords

Main Subjects

References

  1. Nolan E, Lindeman GJ, Visvader JE. Deciphering breast cancer: from biology to the clinic. Cell. 2023;186(8):1708-28.
  2. Zagami P, Carey LA. Triple negative breast cancer: Pitfalls and progress. NPJ breast cancer. 2022;8(1):95.
  3. Li Y, Zhang H, Merkher Y, Chen L, Liu N, Leonov S, et al. Recent advances in therapeutic strategies for triple-negative breast cancer. Journal of hematology & oncology. 2022;15(1):121.
  4. Jin MC, Medress ZA, Azad TD, Doulames VM, Veeravagu A. Stem cell therapies for acute spinal cord injury in humans: a review. Neurosurgical focus. 2019;46(3):E10.
  5. Dong L-H, Jiang Y-Y, Liu Y-J, Cui S, Xia C-C, Qu C, et al. The anti-fibrotic effects of mesenchymal stem cells on irradiated lungs via stimulating endogenous secretion of HGF and PGE2. Scientific Reports. 2015;5(1):8713.
  6. Tu Z, Karnoub AE. Mesenchymal stem/stromal cells in breast cancer development and management. Seminars in cancer biology. 2022;86(Pt 2):81-92.
  7. Liu J, Gao J, Liang Z, Gao C, Niu Q, Wu F, et al. Mesenchymal stem cells and their microenvironment. Stem cell research & therapy. 2022;13(1):429.
  8. Lin Z, Wu Y, Xu Y, Li G, Li Z, Liu T. Mesenchymal stem cell-derived exosomes in cancer therapy resistance: recent advances and therapeutic potential. Molecular cancer. 2022;21(1):179.
  9. Ra K, Park SC, Lee BC. Female Reproductive Aging and Oxidative Stress: Mesenchymal Stem Cell Conditioned Medium as a Promising Antioxidant. International journal of molecular sciences. 2023;24(5).
  10. Alió Del Barrio JL, De la Mata A, De Miguel MP, Arnalich-Montiel F, Nieto-Miguel T, El Zarif M, et al. Corneal Regeneration Using Adipose-Derived Mesenchymal Stem Cells. Cells. 2022;11(16).
  11. Chakraborty S, Rahman T. The difficulties in cancer treatment. Ecancermedicalscience. 2012;6:ed16.
  12. Xuan X, Tian C, Zhao M, Sun Y, Huang C. Mesenchymal stem cells in cancer progression and anticancer therapeutic resistance. Cancer Cell International. 2021;21(1):595.
  13. Al-Ejeh F, Smart CE, Morrison BJ, Chenevix-Trench G, López JA, Lakhani SR, et al. Breast cancer stem cells: treatment resistance and therapeutic opportunities. Carcinogenesis. 2011;32(5):650-8.
  14. He N, Kong Y, Lei X, Liu Y, Wang J, Xu C, et al. MSCs inhibit tumor progression and enhance radiosensitivity of breast cancer cells by down-regulating Stat3 signaling pathway. Cell Death Dis. 2018;9(10):1026-.
  15. Kim J, Hall RR, Lesniak MS, Ahmed AU. Stem Cell-Based Cell Carrier for Targeted Oncolytic Virotherapy: Translational Opportunity and Open Questions. Viruses. 2015;7(12):6200-17.
  16. Cuiffo BG, Karnoub AE. Mesenchymal stem cells in tumor development: emerging roles and concepts. Cell adhesion & migration. 2012;6(3):220-30.
  17. Hmadcha A, Martin-Montalvo A, Gauthier BR, Soria B, Capilla-Gonzalez V. Therapeutic Potential of Mesenchymal Stem Cells for Cancer Therapy. Frontiers in bioengineering and biotechnology. 2020;8:43.
  18. Huo Q, Li K, Sun X, Zhuang A, Minami K, Tamari K, et al. The inhibition of pancreatic cancer progression by K-Ras-overexpressing mesenchymal stem cell-derived secretomes. Scientific Reports. 2023;13(1):15036.
  19. Jahangiri B, Khalaj-Kondori M, Asadollahi E, Purrafee Dizaj L, Sadeghizadeh M. MSC-Derived exosomes suppress colorectal cancer cell proliferation and metastasis via miR-100/mTOR/miR-143 pathway. International journal of pharmaceutics. 2022;627:122214.
  20. Khalil C, Moussa M, Azar A, Tawk J, Habbouche J, Salameh R, et al. Anti-proliferative effects of mesenchymal stem cells (MSCs) derived from multiple sources on ovarian cancer cell lines: an in-vitro experimental study. Journal of ovarian research. 2019;12(1):70.
  21. Zhao J, Zhang Z, Cui Q, Zhao L, Hu Y, Zhao S. Human adipose-derived mesenchymal stem cells inhibit proliferation and induce apoptosis of human gastric cancer HGC-27 cells. 3 Biotech. 2020;10(3):129.
  22. Gentile P. Breast Cancer Therapy: The Potential Role of Mesenchymal Stem Cells in Translational Biomedical Research. Biomedicines. 2022;10(5):1179.
  23. Trivanović D, Nikolić S, Krstić J, Jauković A, Mojsilović S, Ilić V, et al. Characteristics of human adipose mesenchymal stem cells isolated from healthy and cancer affected people and their interactions with human breast cancer cell line MCF-7 in vitro. Cell biology international. 2014;38(2):254-65.
  24. Ahn JO, Coh YR, Lee HW, Shin IS, Kang SK, Youn HY. Human adipose tissue-derived mesenchymal stem cells inhibit melanoma growth in vitro and in vivo. Anticancer research. 2015;35(1):159-68.
  25. Ryu H, Oh JE, Rhee KJ, Baik SK, Kim J, Kang SJ, et al. Adipose tissue-derived mesenchymal stem cells cultured at high density express IFN-β and suppress the growth of MCF-7 human breast cancer cells. Cancer letters. 2014;352(2):220-7.
  26. Kalamegam G, Sait KHW, Anfinan N, Kadam R, Ahmed F, Rasool M, et al. Cytokines secreted by human Wharton's jelly stem cells inhibit the proliferation of ovarian cancer (OVCAR3) cells in vitro. Oncology letters. 2019;17(5):4521-31.
  27. Yang C, Lei D, Ouyang W, Ren J, Li H, Hu J, et al. Conditioned media from human adipose tissue-derived mesenchymal stem cells and umbilical cord-derived mesenchymal stem cells efficiently induced the apoptosis and differentiation in human glioma cell lines in vitro. BioMed research international. 2014;2014:109389.
  28. Li L, Tian H, Chen Z, Yue W, Li S, Li W. Inhibition of lung cancer cell proliferation mediated by human mesenchymal stem cells. Acta biochimica et biophysica Sinica. 2011;43(2):143-8.
  29. Li P, Zhou H, Di G, Liu J, Liu Y, Wang Z, et al. Mesenchymal stem cell-conditioned medium promotes MDA-MB-231 cell migration and inhibits A549 cell migration by regulating insulin receptor and human epidermal growth factor receptor 3 phosphorylation. Oncology letters. 2017;13(3):1581-6.
  30. Xie H, Liao N, Lan F, Cai Z, Liu X, Liu J. 3D-cultured adipose tissue-derived stem cells inhibit liver cancer cell migration and invasion through suppressing epithelial-mesenchymal transition. International journal of molecular medicine. 2018;41(3):1385-96.
  31. Yousef EM, Tahir MR, St-Pierre Y, Gaboury LA. MMP-9 expression varies according to molecular subtypes of breast cancer. BMC cancer. 2014;14:609.
  32. Eckert LB, Repasky GA, Ulkü AS, McFall A, Zhou H, Sartor CI, et al. Involvement of Ras activation in human breast cancer cell signaling, invasion, and anoikis. Cancer research. 2004;64(13):4585-92.
  33. Uprety D, Adjei AA. KRAS: From undruggable to a druggable Cancer Target. Cancer treatment reviews. 2020;89:102070.
  34. Van Sciver RE, Njogu MM, Isbell AJ, Odanga JJ, Bian M, Svyatova E, et al. Chapter 12 - Blocking SIAH Proteolysis, an Important K-RAS Vulnerability, to Control and Eradicate K-RAS-Driven Metastatic Cancer. In: Azmi AS, editor. Conquering RAS. Boston: Academic Press; 2017. p. 213-32.
  35. Gupta GK, Collier AL, Lee D, Hoefer RA, Zheleva V, Siewertsz van Reesema LL, et al. Perspectives on Triple-Negative Breast Cancer: Current Treatment Strategies, Unmet Needs, and Potential Targets for Future Therapies. Cancers. 2020;12(9).
Archives of Razi Institute
Volume 79, Issue 6
November and December 2024
Pages 1249-1256

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