Interleukin-6, -8, and TGF-β Secreted from Mesenchymal Stem Cells Show Functional Role in Reduction of Telomerase Activity of Leukemia Cell Via Wnt5a/β-Catenin and P53 Pathways

Overview

Journal Adv Pharm Bull

Date 2020 May 7

PMID 32373501

Citations 23

Authors

Ezzatollah Fathi

Behnaz Valipour

Zohreh Sanaat

Hojjatollah Nozad Charoudeh

Raheleh Farahzadi

Affiliations

Soon will be listed here.

Abstract

The effect of mesenchymal stem cells (MSCs) on the immortality features of malignant cells, such as hematologic cancerous cells, are controversial, and the associated mechanisms are yet to be well understood. The aim of the present study was to investigate the in vitro effect of bone marrow-derived MSCs (BMSCs) on the chronic myeloid leukemia cell line K562 through telomere length measurements, telomerase activity assessments, and gene expression. The possible signaling pathways involved in this process, including Wnt-5a/β-catenin and P53, were also evaluated. Two cell populations (BMSCs and K562 cell line) were co-cultured on transwell plates for 7 days. Next, K562 cells were collected and subjected to quantitative real-time PCR, PCR-ELISA TRAP assay, and the ELISA sandwich technique for telomere length, gene expression, telomerase activity assay, and cytokine measurement, respectively. Also, the involvement of the mentioned signaling pathways in this process was reported by real-time PCR and Western blotting through gene and protein expression, respectively. The results showed that BMSCs caused significant decreases in telomere length, telomerase activity, and the mRNA level of as a regulator of telomerase activity. The significant presence of interleukin (IL)-6, IL-8, and transforming growth factor beta (TGF-β) was obvious in the co-cultured media. Also, BMSCs significantly decreased and increased the gene and protein expression of β-catenin and P53, respectively. It was concluded that the mentioned effects of IL-6, IL-8, and TGF-β cytokines secreted from MSCs on K562 cells as therapeutic agents were applied by Wnt-5a/β-catenin and P53 pathways.

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References

Wang L, Lu H, Liu P, Fei X, Wu Y, Wang C . [Effect of co-culture of bone marrow mesenchymal stem cells and K562 cells on expression of interleukin 8]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2008; 16(1):156-8. View

Sun T, Sun B, Ni C, Zhao X, Wang X, Qie S . Pilot study on the interaction between B16 melanoma cell-line and bone-marrow derived mesenchymal stem cells. Cancer Lett. 2008; 263(1):35-43. DOI: 10.1016/j.canlet.2007.12.015. View

Miller L, Kurtzman S, Wang Y, Anderson K, LINDQUIST R, Kreutzer D . Expression of interleukin-8 receptors on tumor cells and vascular endothelial cells in human breast cancer tissue. Anticancer Res. 1998; 18(1A):77-81. View

Zhang H, Zhang L . Influence of human bone marrow mesenchymal stem cells on proliferation of chronic myeloid leukemia cells. Ai Zheng. 2009; 28(1):29-32. View

Farahzadi R, Fathi E, Mesbah-Namin S, Zarghami N . Zinc sulfate contributes to promote telomere length extension via increasing telomerase gene expression, telomerase activity and change in the TERT gene promoter CpG island methylation status of human adipose-derived mesenchymal stem cells. PLoS One. 2017; 12(11):e0188052. PMC: 5690675. DOI: 10.1371/journal.pone.0188052. View

Fathi E, Nozad Charoudeh H, Sanaat Z, Farahzadi R . Telomere shortening as a hallmark of stem cell senescence. Stem Cell Investig. 2019; 6:7. PMC: 6458335. DOI: 10.21037/sci.2019.02.04. View

Hoffmeyer K, Raggioli A, Rudloff S, Anton R, Hierholzer A, Del Valle I . Wnt/β-catenin signaling regulates telomerase in stem cells and cancer cells. Science. 2012; 336(6088):1549-54. DOI: 10.1126/science.1218370. View

Mehdizadeh A, Somi M, Darabi M, Farajnia S, Akbarzadeh A, Montazersaheb S . Liposome-mediated RNA interference delivery against Erk1 and Erk2 does not equally promote chemosensitivity in human hepatocellular carcinoma cell line HepG2. Artif Cells Nanomed Biotechnol. 2017; 45(8):1612-1619. DOI: 10.1080/21691401.2016.1269117. View

Montazersaheb S, Kabiri F, Saliani N, Nourazarian A, Biray Avci C, Rahbarghazi R . Prolonged incubation with Metformin decreased angiogenic potential in human bone marrow mesenchymal stem cells. Biomed Pharmacother. 2018; 108:1328-1337. DOI: 10.1016/j.biopha.2018.09.135. View

10.

Secchiero P, Zorzet S, Tripodo C, Corallini F, Melloni E, Caruso L . Human bone marrow mesenchymal stem cells display anti-cancer activity in SCID mice bearing disseminated non-Hodgkin's lymphoma xenografts. PLoS One. 2010; 5(6):e11140. PMC: 2886845. DOI: 10.1371/journal.pone.0011140. View

11.

Fathi E, Farahzadi R, Sheikhzadeh N . Immunophenotypic characterization, multi-lineage differentiation and aging of zebrafish heart and liver tissue-derived mesenchymal stem cells as a novel approach in stem cell-based therapy. Tissue Cell. 2019; 57:15-21. DOI: 10.1016/j.tice.2019.01.006. View

12.

Park C, Kim K, Bae S, Son H, Myung P, Hong H . Cytokine secretion profiling of human mesenchymal stem cells by antibody array. Int J Stem Cells. 2014; 2(1):59-68. PMC: 4021795. DOI: 10.15283/ijsc.2009.2.1.59. View

13.

Choupani J, Nariman-Saleh-Fam Z, Saadatian Z, Ouladsahebmadarek E, Masotti A, Bastami M . Association of mir-196a-2 rs11614913 and mir-149 rs2292832 Polymorphisms With Risk of Cancer: An Updated Meta-Analysis. Front Genet. 2019; 10:186. PMC: 6429108. DOI: 10.3389/fgene.2019.00186. View

14.

Tyndall A, Walker U, Cope A, Dazzi F, De Bari C, Fibbe W . Immunomodulatory properties of mesenchymal stem cells: a review based on an interdisciplinary meeting held at the Kennedy Institute of Rheumatology Division, London, UK, 31 October 2005. Arthritis Res Ther. 2007; 9(1):301. PMC: 1860056. DOI: 10.1186/ar2103. View

15.

Klassen H, Imfeld K, Kirov I, Tai L, Gage F, Young M . Expression of cytokines by multipotent neural progenitor cells. Cytokine. 2003; 22(3-4):101-6. DOI: 10.1016/s1043-4666(03)00120-0. View

16.

Keller G, Brassat U, Braig M, Heim D, Wege H, Brummendorf T . Telomeres and telomerase in chronic myeloid leukaemia: impact for pathogenesis, disease progression and targeted therapy. Hematol Oncol. 2009; 27(3):123-9. DOI: 10.1002/hon.901. View

17.

Wenn K, Tomala L, Wilop S, Vankann L, Hasenbank C, Frank O . Telomere length at diagnosis of chronic phase chronic myeloid leukemia (CML-CP) identifies a subgroup with favourable prognostic parameters and molecular response according to the ELN criteria after 12 months of treatment with nilotinib. Leukemia. 2015; 29(12):2402-4. DOI: 10.1038/leu.2015.245. View

18.

Liu C, Hwang S . Cytokine interactions in mesenchymal stem cells from cord blood. Cytokine. 2005; 32(6):270-9. DOI: 10.1016/j.cyto.2005.11.003. View

19.

Montazersaheb S, Kazemi M, Nabat E, Nielsen P, Hejazi M . Downregulation of TdT Expression through Splicing Modulation by Antisense Peptide Nucleic Acid (PNA). Curr Pharm Biotechnol. 2019; 20(2):168-178. DOI: 10.2174/1389201020666190206202650. View

20.

Fonseka M, Ramasamy R, Tan B, Seow H . Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSC) inhibit the proliferation of K562 (human erythromyeloblastoid leukaemic cell line). Cell Biol Int. 2012; 36(9):793-801. DOI: 10.1042/CBI20110595. View