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Updated: Jun 12, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
Targeting the Transforming Growth Factor-beta pathway inhibits human basal-like breast cancer metastasis
Vidya Ganapathy1, Rongrong Ge, Alison Grazioli
1Division of Medical Oncology, Department of Internal Medicine, UMDNJRobert Wood Johnson Medical School and The Cancer Institute of New Jersey, New Brunswick, NJ, USA.
Background:
Transforming Growth Factor beta (TGF-beta) plays an important role in tumor invasion and metastasis. We set out to investigate the possible clinical utility of TGF-beta antagonists in a human metastatic basal-like breast cancer model. We examined the effects of two types of the TGF-beta pathway antagonists (1D11, a mouse monoclonal pan-TGF-beta neutralizing antibody and LY2109761, a chemical inhibitor of TGF-beta type I and II receptor kinases) on sublines of basal cell-like MDA-MB-231 human breast carcinoma cells that preferentially metastasize to lungs (4175TR, 4173) or bones (SCP2TR, SCP25TR, 2860TR, 3847TR).
Results:
Both 1D11 and LY2109761 effectively blocked TGF-beta-induced phosphorylation of receptor-associated Smads in all MDA-MB-231 subclones in vitro. Moreover, both antagonists inhibited TGF-beta stimulated in vitro migration and invasiveness of MDA-MB-231 subclones, indicating that these processes are partly driven by TGF-beta. In addition, both antagonists significantly reduced the metastatic burden to either lungs or bones in vivo, seemingly independently of intrinsic differences between the individual tumor cell clones. Besides inhibiting metastasis in a tumor cell autonomous manner, the TGF-beta antagonists inhibited angiogenesis associated with lung metastases and osteoclast number and activity associated with lytic bone metastases. In aggregate, these studies support the notion that TGF-beta plays an important role in both bone-and lung metastases of basal-like breast cancer, and that inhibiting TGF-beta signaling results in a therapeutic effect independently of the tissue-tropism of the metastatic cells. Targeting the TGF-beta pathway holds promise as a novel therapeutic approach for metastatic basal-like breast cancer.
Conclusions:
In aggregate, these studies support the notion that TGF-beta plays an important role in both bone-and lung metastases of basal-like breast cancer, and that inhibiting TGF-beta signaling results in a therapeutic effect independently of the tissue-tropism of the metastatic cells. Targeting the TGF-beta pathway holds promise as a novel therapeutic approach for metastatic basal-like breast cancer.
Insights
Transforming Growth Factor beta (TGF-beta) antagonists effectively reduced metastasis in basal-like breast cancer models. Inhibiting TGF-beta signaling offers a promising therapeutic strategy for both bone and lung metastases.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Metastasis Research
Background:
- Transforming Growth Factor beta (TGF-beta) is implicated in tumor invasion and metastasis.
- Basal-like breast cancer models are crucial for understanding metastatic processes.
- TGF-beta antagonists are being explored for their clinical utility.
Purpose of the Study:
- To investigate the clinical utility of TGF-beta antagonists in a human metastatic basal-like breast cancer model.
- To examine the effects of two TGF-beta pathway antagonists on MDA-MB-231 breast carcinoma cell sublines.
- To assess the impact of TGF-beta inhibition on lung and bone metastasis.
Main Methods:
- Utilized two TGF-beta pathway antagonists: 1D11 (monoclonal antibody) and LY2109761 (kinase inhibitor).
- Tested antagonists on MDA-MB-231 sublines with preferential lung or bone metastasis.
- Evaluated in vitro migration, invasiveness, and in vivo metastatic burden.
Main Results:
- Both antagonists blocked TGF-beta-induced Smad phosphorylation in vitro.
- Inhibitors reduced MDA-MB-231 cell migration and invasiveness.
- Significant reduction in lung and bone metastatic burden observed in vivo.
- TGF-beta antagonists also inhibited angiogenesis and osteoclast activity.
Conclusions:
- TGF-beta plays a critical role in both bone and lung metastases of basal-like breast cancer.
- Inhibiting TGF-beta signaling yields therapeutic effects regardless of metastatic tissue tropism.
- Targeting the TGF-beta pathway presents a promising novel therapeutic approach for metastatic basal-like breast cancer.
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