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Updated: Apr 18, 2026
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Endoglin silencing has significant antitumor effect on murine mammary adenocarcinoma mediated by vascular targeted
Tanja Dolinsek, Bostjan Markelc, Masa Bosnjak
1Institute of Oncology Ljubljana, Zaloska 2, 1000 Ljubljana, Slovenia. mcemazar@onko-i.si.
Abstract:
New targets and therapeutic approaches for vascular targeted strategies in oncology are continuously explored. Endoglin, a co-receptor of TGF-β, is a known target, however, its silencing with vector-based RNA interference technology has not been evaluated yet. Therefore, in our study, we assembled plasmid DNA coding for shRNA against endoglin, and used gene electrotransfer as a delivery method to determine its antitumor and vascular targeted effects. In vitro and in vivo data provide evidence of vascular targeted effects of endoglin silencing. The vascular targeted action of endoglin silencing could be described as a result of two separated effect; antiangiogenic and vascular disrupting effect. This was first supported by in vitro data; predominantly by reduction of proliferation and tube formation of endothelial cells. In the TS/A murine mammary carcinoma model, in which the tumor cells do not express endoglin, reduced tumor growth and number of vessels were observed. Quick destruction of existing activated blood vessels at the site of tumor cells' injection and sustained growth of tumors afterwards was observed in tumors that were growing in dorsal window chamber by intravital microscopy. This observation supports both vascular disrupting and antiangiogenic action. In conclusion, the results of our study provide evidence of endoglin as a valid target for cancer therapy and support further development of plasmid shRNA delivery, which have prolonged antitumor effect, especially in combined schedules.
Insights
Endoglin silencing using gene electrotransfer demonstrated significant antitumor and vascular-disrupting effects in preclinical cancer models. This approach offers a promising new strategy for vascular-targeted cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Vascular Biology
Background:
- Endoglin (CD105) is a TGF-β co-receptor and a validated target for vascular-targeted cancer therapy.
- Vector-based RNA interference for endoglin silencing has not been previously investigated.
Purpose of the Study:
- To evaluate the antitumor and vascular-targeted effects of endoglin silencing using plasmid-based short hairpin RNA (shRNA) delivered via gene electrotransfer.
- To elucidate the mechanisms underlying endoglin silencing's vascular-targeted action.
Main Methods:
- Construction of plasmid DNA encoding shRNA targeting endoglin.
- Delivery of plasmid DNA using gene electrotransfer in vitro and in vivo.
- Assessment of endothelial cell proliferation and tube formation.
- Evaluation of tumor growth, vascularization, and blood vessel dynamics in a murine mammary carcinoma model using intravital microscopy.
Main Results:
- Endoglin silencing reduced endothelial cell proliferation and tube formation in vitro.
- In vivo, endoglin silencing led to reduced tumor growth and decreased vessel density in the TS/A murine mammary carcinoma model.
- Intravital microscopy revealed rapid destruction of existing tumor vasculature and sustained tumor growth, supporting both anti-angiogenic and vascular-disrupting effects.
Conclusions:
- Endoglin is a viable therapeutic target for cancer treatment.
- Plasmid-based shRNA delivery via gene electrotransfer demonstrates prolonged antitumor effects.
- This approach holds potential for combination therapies in cancer treatment.
