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Osteopontin mediates an MZF1-TGF-β1-dependent transformation of mesenchymal stem cells into cancer-associated fibroblasts in breast cancer.

Publication ,  Journal Article
Weber, CE; Kothari, AN; Wai, PY; Li, NY; Driver, J; Zapf, MAC; Franzen, CA; Gupta, GN; Osipo, C; Zlobin, A; Syn, WK; Zhang, J; Kuo, PC; Mi, Z
Published in: Oncogene
September 10, 2015

Interactions between tumor cells and cancer-associated fibroblasts (CAFs) in the tumor microenvironment significantly influence cancer growth and metastasis. Transforming growth factor-β (TGF-β) is known to be a critical mediator of the CAF phenotype, and osteopontin (OPN) expression in tumors is associated with more aggressive phenotypes and poor patient outcomes. The potential link between these two pathways has not been previously addressed. Utilizing in vitro studies using human mesenchymal stem cells (MSCs) and MDA-MB231 (OPN+) and MCF7 (OPN-) human breast cancer cell lines, we demonstrate that OPN induces integrin-dependent MSC expression of TGF-β1 to mediate adoption of the CAF phenotype. This OPN-TGF-β1 pathway requires the transcription factor, myeloid zinc finger 1 (MZF1). In vivo studies with xenotransplant models in NOD-scid mice showed that OPN expression increases cancer growth and metastasis by mediating MSC-to-CAF transformation in a process that is MZF1 and TGF-β1 dependent. We conclude that tumor-derived OPN engenders MSC-to-CAF transformation in the microenvironment to promote tumor growth and metastasis via the OPN-MZF1-TGF-β1 pathway.

Duke Scholars

Published In

Oncogene

DOI

EISSN

1476-5594

Publication Date

September 10, 2015

Volume

34

Issue

37

Start / End Page

4821 / 4833

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Transforming Growth Factor beta1
  • Signal Transduction
  • Osteopontin
  • Oncology & Carcinogenesis
  • Neoplastic Stem Cells
  • Mice, SCID
  • Mice, Inbred NOD
  • Mice
  • Mesenchymal Stem Cells
 

Citation

APA
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MLA
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Weber, C. E., Kothari, A. N., Wai, P. Y., Li, N. Y., Driver, J., Zapf, M. A. C., … Mi, Z. (2015). Osteopontin mediates an MZF1-TGF-β1-dependent transformation of mesenchymal stem cells into cancer-associated fibroblasts in breast cancer. Oncogene, 34(37), 4821–4833. https://doi.org/10.1038/onc.2014.410
Weber, C. E., A. N. Kothari, P. Y. Wai, N. Y. Li, J. Driver, M. A. C. Zapf, C. A. Franzen, et al. “Osteopontin mediates an MZF1-TGF-β1-dependent transformation of mesenchymal stem cells into cancer-associated fibroblasts in breast cancer.Oncogene 34, no. 37 (September 10, 2015): 4821–33. https://doi.org/10.1038/onc.2014.410.
Weber CE, Kothari AN, Wai PY, Li NY, Driver J, Zapf MAC, et al. Osteopontin mediates an MZF1-TGF-β1-dependent transformation of mesenchymal stem cells into cancer-associated fibroblasts in breast cancer. Oncogene. 2015 Sep 10;34(37):4821–33.
Weber, C. E., et al. “Osteopontin mediates an MZF1-TGF-β1-dependent transformation of mesenchymal stem cells into cancer-associated fibroblasts in breast cancer.Oncogene, vol. 34, no. 37, Sept. 2015, pp. 4821–33. Pubmed, doi:10.1038/onc.2014.410.
Weber CE, Kothari AN, Wai PY, Li NY, Driver J, Zapf MAC, Franzen CA, Gupta GN, Osipo C, Zlobin A, Syn WK, Zhang J, Kuo PC, Mi Z. Osteopontin mediates an MZF1-TGF-β1-dependent transformation of mesenchymal stem cells into cancer-associated fibroblasts in breast cancer. Oncogene. 2015 Sep 10;34(37):4821–4833.

Published In

Oncogene

DOI

EISSN

1476-5594

Publication Date

September 10, 2015

Volume

34

Issue

37

Start / End Page

4821 / 4833

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Transforming Growth Factor beta1
  • Signal Transduction
  • Osteopontin
  • Oncology & Carcinogenesis
  • Neoplastic Stem Cells
  • Mice, SCID
  • Mice, Inbred NOD
  • Mice
  • Mesenchymal Stem Cells