{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T23:10:56Z","timestamp":1785798656764,"version":"3.56.0"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,18]],"date-time":"2021-10-18T00:00:00Z","timestamp":1634515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> 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.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Mesenchymal stem cells with CAF-like phenotype were obtained by treating MSCs with recombinant human transforming growth factor-\u03b2 (rhTGF-\u03b2), hereafter referred to as TGF-\u03b2 conditioned MSCs. <jats:italic>In vivo<\/jats:italic> mouse model experiments, <jats:italic>in vitro<\/jats:italic> 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-\u03b2 conditioned MSCs and leukemia cells in promoting the growth, migration and invasion of B-ALL cells.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Compared with untreated MSCs, TGF-\u03b2 conditioned MSCs significantly promoted the growth and proliferation of leukemia cells in mice, and increased the expression of CXCR4 in tumor tissues. <jats:italic>In vitro<\/jats:italic> cell experiments, TGF-\u03b2 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-\u03b2 conditioned MSCs and inhibiting the activation of the PI3K\/AKT signaling pathway in leukemia cells. Further, findings were made that the interaction between TGF-\u03b2 conditioned MSCs and leukemia cells were mediated by the interaction between the integrin receptor \u03b15\u03b21 on the surface of leukemia cells and the increased expression of fibronectin on TGF-\u03b2 conditioned MSCs. AMD3100 could weaken such effect by reducing the expression of integrin \u03b15\u03b21 on leukemia cells. Further regulation of integrin \u03b21 could effectively interfere with the interaction between TGF-\u03b2 conditioned MSCs and leukemia cells.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> 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 \u03b21 might be a potential therapeutic strategy.<\/jats:p>","DOI":"10.3389\/fcell.2021.708513","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T00:04:31Z","timestamp":1634688271000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["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"],"prefix":"10.3389","volume":"9","author":[{"given":"Chengyun","family":"Pan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyun","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luxin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingzhen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianzhen","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jishi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.matbio.2020.05.004","article-title":"Cancer associated fibroblast: mediators of tumorigenesis.","volume":"9","author":"Alexander","year":"2020","journal-title":"Matrix Biol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2022","DOI":"10.3892\/or.2018.6254","article-title":"CXCR4 receptor blockage reduces the contribution of tumor and stromal cells to the metastatic growth in the liver.","volume":"39","author":"Benedicto","year":"2018","journal-title":"Oncol. 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