Data_Sheet_1_Mesenchymal Stem Cells With Cancer-Associated Fibroblast-Like Phenotype Stimulate SDF-1/CXCR4 Axis to Enhance the Growth and Invasion of B-Cell Acute Lymphoblastic Leukemia Cells Through Cell-to-Cell Communication.zip
Background: Bone marrow mesenchymal stem cells (BM-MSCs) are the stromal cells in the leukemia microenvironment, and can obtain cancer-associated fibroblast (CAF)-like phenotype under certain conditions to further promote leukemia progression. However, the mechanism of MSCs with CAF-like phenotype interacting with leukemia cells in B-cell acute lymphoblastic leukemia (B-ALL) and promoting the progression of B-ALL remains unclear.
Methods: Mesenchymal stem cells with CAF-like phenotype were obtained by treating MSCs with recombinant human transforming growth factor-β (rhTGF-β), hereafter referred to as TGF-β conditioned MSCs. In vivo mouse model experiments, in vitro transwell chamber experiments, three-dimensional (3D) cell culture models, lentiviral transfection and other experimental methods were used to investigate the possible mechanism of the interaction between TGF-β conditioned MSCs and leukemia cells in promoting the growth, migration and invasion of B-ALL cells.
Results: Compared with untreated MSCs, TGF-β conditioned MSCs significantly promoted the growth and proliferation of leukemia cells in mice, and increased the expression of CXCR4 in tumor tissues. In vitro cell experiments, TGF-β conditioned MSCs obviously promoted the migration and invasion of Nalm-6/RS4;11 cells, which were effectively blocked by the CXCR4 inhibitor AMD3100, thereby inhibiting the secretion of MMP-9 in TGF-β conditioned MSCs and inhibiting the activation of the PI3K/AKT signaling pathway in leukemia cells. Further, findings were made that the interaction between TGF-β conditioned MSCs and leukemia cells were mediated by the interaction between the integrin receptor α5β1 on the surface of leukemia cells and the increased expression of fibronectin on TGF-β conditioned MSCs. AMD3100 could weaken such effect by reducing the expression of integrin α5β1 on leukemia cells. Further regulation of integrin β1 could effectively interfere with the interaction between TGF-β conditioned MSCs and leukemia cells.
Conclusion: Mesenchymal stem cells with CAF-like phenotype could be a key factor in promoting the growth and invasion of B-ALL cells, and the SDF-1/CXCR4 axis might be a significant factor in mediating the communication of MSCs with CAF-like phenotype and leukemia cells. To prevent the progression of B-ALL cells, blocking the SDF-1/CXCR4 axis with AMD3100 or targeting integrin β1 might be a potential therapeutic strategy.
History
References
- https://doi.org//10.1016/j.matbio.2020.05.004
- https://doi.org//10.3892/or.2018.6254
- https://doi.org//10.3324/haematol.2016.157883
- https://doi.org//10.1182/blood.2019001398
- https://doi.org//10.1073/pnas.1815515116
- https://doi.org//10.1016/j.bbamcr.2015.08.015
- https://doi.org//10.1007/978-1-0716-0779-4_19
- https://doi.org//10.1002/pbc.26414
- https://doi.org//10.1046/j.1365-2141.2001.03164.x
- https://doi.org//10.3390/ijms22094426
- https://doi.org//10.1007/s00018-014-1830-x
- https://doi.org//10.1200/EDBK_280175
- https://doi.org//10.3389/fonc.2020.606540
- https://doi.org//10.1080/10428190903150847
- https://doi.org//10.1016/j.ccr.2014.04.015
- https://doi.org//10.1083/jcb.201704053
- https://doi.org//10.1021/acs.analchem.1c00469
- https://doi.org//10.1038/leu.2015.289
- https://doi.org//10.2147/BLCTT.S170351
- https://doi.org//10.7150/ijms.50080
- https://doi.org//10.3390/cancers11050721
- https://doi.org//10.1002/ajh.25099
- https://doi.org//10.3390/cancers13061399
- https://doi.org//10.1111/j.1365-2141.2009.07648.x
- https://doi.org//10.1038/sj.leu.2404684
- https://doi.org//10.14670/HH-11-700
- https://doi.org//10.18632/oncotarget.26720
- https://doi.org//10.1186/s12935-018-0578-z
- https://doi.org//10.1007/s13238-011-1097-z
- https://doi.org//10.1016/j.gene.2020.144726
- https://doi.org//10.1111/cas.14664
- https://doi.org//10.1007/s00432-015-2046-7
- https://doi.org//10.1016/j.biopha.2020.110610
- https://doi.org//10.1111/j.1582-4934.2010.01044.x
- https://doi.org//10.3390/ijms20020412
- https://doi.org//10.1007/s00018-016-2306-y
- https://doi.org//10.1016/j.blre.2017.03.004
- https://doi.org//10.26355/eurrev_202009_22994
- https://doi.org//10.1098/rsif.2019.0226
- https://doi.org//10.1080/15384047.2019.1685157
- https://doi.org//10.1158/0008-5472.can-03-3693
- https://doi.org//10.1186/s13045-015-0231-4
- https://doi.org//10.3892/ol.2019.10188
- https://doi.org//10.1111/bjh.12883
- https://doi.org//10.2147/OTT.S249425
- https://doi.org//10.17219/acem/70418
- https://doi.org//10.1016/j.exphem.2012.11.004
- https://doi.org//10.1016/j.pharmthera.2020.107753
- https://doi.org//10.2147/DDDT.S84932
- https://doi.org//10.1155/2021/6683391
- https://doi.org//10.1186/s13046-016-0405-0
- https://doi.org//10.21037/atm-20-4843
- https://doi.org//10.3390/biology9100328
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