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Updated: Jul 31, 2026

Monitoring Functionality and Morphology of Vasculature Recruited by Factors Secreted by Fast-growing Tumor-generating Cells
Published on: November 23, 2014
FTY720 inhibits tumor growth and angiogenesis
1Department of Surgery, University of Munich, Klinikum Grosshadern, Munich, Germany.
Abstract:
De novo malignancies and recurrence of tumors are some of the biggest threats to allograft recipients subjected to chronic immunosuppression. FTY720, a synthetic myriocin analogue, is an immunosuppressant that induces apoptosis of activated lymphocytes and prevents infiltration of lymphocytes into allografts, thereby prolonging allograft survival in a dose-dependent manner. Additionally, FTY720 was shown to prevent tumor growth and metastasis. Therefore, we examined the effect of FTY720 on angiogenesis in a HUVEC spheroid model. To substantiate our in vitro findings the effect of FTY720 was also tested in C57/B16 mice subcutaneously injected with Lewis Lung Carcinoma (LLC1) cells. After establishment of a palpable tumor the animals were treated daily with either saline or 1, 5, or 10 mg/kg FTY720. Subsequently, the tumor size was measured, periodically. In our experiments FTY720 showed a strong antiangiogenic effect, overcoming the stimulating effect of VEGF (20 ng/mL) even at subnanomolar concentrations. In vivo, FTY720 showed a dose-dependent inhibition of subcutaneous tumors, and the tumor size of animals treated with 10 mg/kg FTY720 was less than half of the size of tumors in control animals. In conclusion, FTY-720 demonstrated a strong antiangiogenic effect in vitro and a substantial antitumor effect in vivo. Presumably, the stabilizing effect of surrounding pericytes limits the effect of FTY720 in our mouse model. Therefore, a combination of FTY720 with an mTOR inhibitor might be the most favorable immunosuppressive drug combination for allograft recipients at risk for tumor development.
Insights
FTY720, an immunosuppressant, demonstrated significant antiangiogenic and antitumor effects in vitro and in vivo. This drug may offer a promising therapeutic strategy for allograft recipients prone to tumor development.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- De novo malignancies and tumor recurrence pose significant risks for allograft recipients undergoing chronic immunosuppression.
- FTY720, a synthetic myriocin analogue, is an immunosuppressant known to prolong allograft survival by inducing lymphocyte apoptosis and preventing infiltration.
- Previous studies indicated FTY720's potential in preventing tumor growth and metastasis.
Purpose of the Study:
- To investigate the antiangiogenic effects of FTY720 using a human umbilical vein endothelial cell (HUVEC) spheroid model.
- To evaluate the in vivo antitumor efficacy of FTY720 in a murine Lewis Lung Carcinoma (LLC1) model.
Main Methods:
- In vitro: Assessed FTY720's effect on angiogenesis in HUVEC spheroids, including its interaction with vascular endothelial growth factor (VEGF).
- In vivo: Administered daily doses of FTY720 (1, 5, or 10 mg/kg) or saline to C57/B16 mice bearing subcutaneous LLC1 tumors.
- Monitored tumor size periodically after palpable tumor establishment.
Main Results:
- FTY720 exhibited a potent antiangiogenic effect in vitro, counteracting VEGF-induced stimulation even at subnanomolar concentrations.
- In vivo, FTY720 demonstrated dose-dependent inhibition of subcutaneous tumor growth.
- Tumor size in mice treated with 10 mg/kg FTY720 was reduced by more than 50% compared to control animals.
Conclusions:
- FTY720 possesses significant antiangiogenic and antitumor properties.
- The pericyte-stabilizing effect may limit FTY720's efficacy in this specific mouse model.
- Combining FTY720 with an mTOR inhibitor could be an optimal immunosuppressive strategy for at-risk allograft recipients.
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