FTY720 inhibits tumor growth and angiogenesis

G Schmid1, M Guba, A Papyan

  • 1Department of Surgery, University of Munich, Klinikum Grosshadern, Munich, Germany.

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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