Difference of interferon-α and interferon-β on melanoma growth and lymph node metastasis in mice.
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.
Department of Dermatology and Cutaneous Biology Research Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Mi Ryung
MR
Roh
Zhenlong
Z
Zheng
Hyun Sook
HS
Kim
Hei-Cheul
HC
Jeung
Sun Young
SY
Rha
Kee Yang
KY
Chung
D000818:Animals; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D000068556:Interferon beta-1a; D016898:Interferon-alpha / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D008207:Lymphatic Metastasis; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011897:Random Allocation; D011994:Recombinant Proteins / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D016899:Interferon-beta; D000068556:Interferon beta-1a