Related Experiment Video
Updated: Dec 26, 2025
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Inhibition of Endoglin Exerts Antitumor Effects through the Regulation of Non-Smad TGF-β Signaling in Angiosarcoma
Ryoko Sakamoto1, Ikko Kajihara1, Hitomi Miyauchi1
1Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Abstract:
Angiosarcoma is a rare malignant tumor derived from endothelial cells, and its prognosis is poor because advanced angiosarcoma is often resistant to taxane therapy. Endoglin (CD105) acts as a coreceptor for TGF-β signaling and is overexpressed in tumor-associated endothelial cells and enhances tumor angiogenesis. Numerous clinical trials are testing the effectiveness of anti-endoglin antibodies in various types of malignancies. Here, we investigated the role of endoglin in the pathogenesis of angiosarcoma and whether endoglin inhibition results in antitumor activity. Endoglin was overexpressed in angiosarcoma, and its inhibition was effective in promoting apoptosis and the suppression of migration, invasion, tube formation, and Warburg effect in angiosarcoma cells. Knockdown of endoglin activated caspase 3/7 that is essential for apoptosis, reduced survivin levels, and decreased paxillin and vascular endothelial cadherin phosphorylation and matrix metalloproteinase 2 and matrix metalloproteinase 9 activities in angiosarcoma cells. Although endoglin is a coreceptor that regulates TGF-β signaling, the antitumor effect of endoglin in angiosarcoma was not based on Smad signaling regulation but on non-Smad TGF-β signaling. Taken together, these results indicated that endoglin could be a novel therapeutic target for angiosarcoma.
Insights
Endoglin (CD105) is overexpressed in angiosarcoma, a rare cancer. Inhibiting endoglin shows promise as a new therapy by reducing tumor growth and spread.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Angiosarcoma is a rare endothelial cell cancer with poor prognosis, often resistant to chemotherapy.
- Endoglin (CD105), a TGF-β signaling coreceptor, is overexpressed in tumor vasculature and promotes angiogenesis.
- Existing research explores anti-endoglin antibodies for various cancers, suggesting therapeutic potential.
Purpose of the Study:
- To investigate the role of endoglin in angiosarcoma development.
- To determine if endoglin inhibition exhibits antitumor activity in angiosarcoma.
- To elucidate the signaling pathways involved in endoglin's therapeutic effects.
Main Methods:
- Assessed endoglin expression in angiosarcoma tissues.
- Utilized endoglin inhibition (e.g., knockdown) in angiosarcoma cell models.
- Analyzed effects on apoptosis, cell migration, invasion, tube formation, and the Warburg effect.
- Investigated downstream signaling pathways, including Smad and non-Smad TGF-β signaling.
Main Results:
- Endoglin is significantly overexpressed in angiosarcoma.
- Endoglin inhibition suppressed migration, invasion, tube formation, and the Warburg effect.
- Knockdown of endoglin induced apoptosis via caspase 3/7 activation and reduced survivin levels.
- Antitumor effects were mediated through non-Smad TGF-β signaling, not Smad pathways.
Conclusions:
- Endoglin plays a crucial role in angiosarcoma pathogenesis.
- Targeting endoglin demonstrates significant antitumor activity in angiosarcoma models.
- Endoglin represents a promising novel therapeutic target for angiosarcoma treatment.
More Related Videos
Related Concept Videos
01:24Regulation of Angiogenesis and Blood Supply
01:16TGF - β Signaling Pathway
02:38Mitogens and the Cell Cycle