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Updated: May 23, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

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Gr-1+CD11b+ cells are responsible for tumor promoting effect of TGF-β in breast cancer progression

Zhaoyang Li1, Yanli Pang, Sudheer Kumar Gara

  • 1Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20876-4258, USA.

International Journal of Cancer
|April 11, 2012
PubMed

Insights

Myeloid-derived suppressor cells mediate TGF-β

Area of Science:

  • Oncology
  • Immunology
  • Cancer Biology

Background:

  • Transforming growth factor-beta (TGF-β) exhibits dual roles in cancer, acting as both a tumor suppressor and promoter.
  • Mechanisms underlying TGF-β's context-dependent functions require further investigation for effective targeted therapies.

Purpose of the Study:

  • To elucidate the role of myeloid-derived suppressor cells (MDSCs) in TGF-β-mediated mammary tumor progression.
  • To investigate the impact of TGF-β neutralization on MDSCs and their contribution to metastasis.

Main Methods:

  • Utilized the 4T1 mammary tumor model in mice, known for spontaneous lung metastasis.
  • Administered TGF-β neutralizing antibody (1D11) and assessed changes in MDSC populations (Gr-1+CD11b+).
  • Analyzed MDSC apoptosis, Th2 cytokine expression, Arginase 1 levels, and correlation with tumor burden and metastasis.

Main Results:

  • Depletion of Gr-1+CD11b+ cells (MDSCs) reduced the efficacy of TGF-β neutralization therapy.
  • TGF-β neutralization with 1D11 antibody decreased MDSC numbers in tumors and pre-metastatic lungs via apoptosis.
  • 1D11 treatment also reduced Th2 cytokines and Arginase 1 expression, with MDSC levels correlating to tumor size and metastasis.

Conclusions:

  • TGF-β neutralization efficacy is dependent on the presence of Gr-1+CD11b+ myeloid-derived suppressor cells.
  • MDSCs are key mediators in TGF-β's regulation of mammary tumor progression and metastasis.
  • Gr-1+CD11b+ cells show potential as biomarkers for predicting response to TGF-β-targeted therapy.

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