Mesenchymal stem cells play a potential role in regulating the establishment and maintenance of epithelial-mesenchymal transition in MCF7 human breast cancer cells by paracrine and induced autocrine TGF-β

  • Authors:
    • Qilin Xu
    • Liang Wang
    • Hongling Li
    • Qin Han
    • Jing  Li
    • Xuebin  Qu
    • Shan Huang
    • Robert Chunhua Zhao
  • View Affiliations

  • Published online on: July 3, 2012     https://doi.org/10.3892/ijo.2012.1541
  • Pages: 959-968
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Abstract

Although the epithelial-mesenchymal transition (EMT) is a normal process that occurs during development, it is thought to be associated with cancer progression and metastasis. Emerging evidence links mesenchymal stem cells (MSCs) in the tumor microenvironment with the occurrence of EMT in cancer progression. In this study, the human breast cancer cell line MCF7 was co-cultured with human adipose-derived MSCs (hAD-MSCs) in a transwell system. Co-cultured cells were analyzed for changes in cellular morphology, EMT markers, protein expression and tumor characteristics. We found that co-cultured MCF7 cells underwent EMT and established a stable mesenchymal phenotype after prolonged co-culturing. Here, we demonstrate that paracrine transforming growth factor-β1 (TGF-β1) secreted by hAD-MSCs regulated the establishment of EMT in MCF7 cells by targeting the ZEB/miR-200 regulatory loop. The downregulation of paracrine TGF-β1 levels can inhibit and reverse the EMT progress by downregulating ZEB1/2 and upregulating miR-200b and miR-200c. The maintenance of a stable mesenchymal state by MCF7 cells required the establishment of autocrine TGF-β signaling to drive and sustain ZEB expression, which had been initiated by the prolonged co-culturing with hAD-MSCs. These results suggest that MSCs may promote breast cancer metastasis by stimulating and facilitating the EMT process.
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September 2012
Volume 41 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Xu Q, Wang L, Li H, Han Q, Li J, Qu X, Huang S and Zhao RC: Mesenchymal stem cells play a potential role in regulating the establishment and maintenance of epithelial-mesenchymal transition in MCF7 human breast cancer cells by paracrine and induced autocrine TGF-β. Int J Oncol 41: 959-968, 2012
APA
Xu, Q., Wang, L., Li, H., Han, Q., Li, J., Qu, X. ... Zhao, R.C. (2012). Mesenchymal stem cells play a potential role in regulating the establishment and maintenance of epithelial-mesenchymal transition in MCF7 human breast cancer cells by paracrine and induced autocrine TGF-β. International Journal of Oncology, 41, 959-968. https://doi.org/10.3892/ijo.2012.1541
MLA
Xu, Q., Wang, L., Li, H., Han, Q., Li, J., Qu, X., Huang, S., Zhao, R. C."Mesenchymal stem cells play a potential role in regulating the establishment and maintenance of epithelial-mesenchymal transition in MCF7 human breast cancer cells by paracrine and induced autocrine TGF-β". International Journal of Oncology 41.3 (2012): 959-968.
Chicago
Xu, Q., Wang, L., Li, H., Han, Q., Li, J., Qu, X., Huang, S., Zhao, R. C."Mesenchymal stem cells play a potential role in regulating the establishment and maintenance of epithelial-mesenchymal transition in MCF7 human breast cancer cells by paracrine and induced autocrine TGF-β". International Journal of Oncology 41, no. 3 (2012): 959-968. https://doi.org/10.3892/ijo.2012.1541