Difference of interferon-α and interferon-β on melanoma growth and lymph node metastasis in mice

Abstract

Interferon (IFN)-α and IFN-β are type I IFNs which are known to exert an antitumor effect on malignant melanoma. The aim of this study was to evaluate and compare the efficacy of IFN-α2b and IFN-β1a on primary tumor growth and lymph node metastasis, and to examine the mechanisms of lymph node metastasis. The efficacy of IFN-α2b and IFN-β1a was evaluated using a human melanoma xenograft model. We further examined the effect of IFNs on lymphangiogenic growth factors in human melanoma cells. IFN-β1a showed a stronger antiproliferative and proapoptotic effect, whereas IFN-α2b inhibited tumor growth and lymph node metastasis through inhibition of lymphangiogenesis. Both IFN-α2b and IFN-β1a were effective in inhibiting lymph node metastasis compared with the control. Microvessel density decreased in tumors treated with IFN-α2b and IFN-β1a compared with the control, without statistical significance. Lymphatic vessel density decreased significantly only in tumors treated with IFN-α2b (P<0.05). Both IFN-α2b and IFN-β1a decreased in-vitro and in-vivo vascular endothelial growth factor (VEGF)-C and VEGF receptor-3 protein expression and secretory VEGF-C level in vitro. IFN-α2b showed an earlier and sustained effect in decreasing VEGF-C and VEGF receptor-3 protein expression and a superior effect in decreasing the secretory VEGF-C level compared with IFN-β1a. Our investigation shows that both IFN-α2b and IFN-β1a exerted different antitumor and antimetastatic effects in human melanoma xenograft. Moreover, the present findings indicate that inhibition of lymphangiogenesis is another possible antimetastatic action mechanism of IFN-α2b.