Satomi Hisae, Wang Binghe, Fujisawa Hiroshi, Otsuka Fujio
Department of Dermatology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
Cytokine. 2002 Apr 21;18(2):108-15. doi: 10.1006/cyto.2002.1028.
Interferon (IFN)-alpha and IFN-beta have been utilized in the treatment of melanoma as a form of cytokine therapy. While previous studies have demonstrated that melanocytes and melanoma cells produce a number of cytokines, it remains unclear whether or not melanocytes and melanoma cells per se produce IFN-alpha or IFN-beta. In the present study, we investigated the expression of IFN-alpha or IFN-beta in human melanocytes and five melanoma cell lines: G-361, C32TG, MMAc, MEWO and VMRC-MELG at both mRNA and protein levels. Both IFN-alpha and IFN-beta mRNA were detected in normal human melanocytes. Likewise, IFN-alpha mRNA was detected in all five melanoma cell lines. However, IFN-beta mRNA was only detected in one melanoma cell line, VMRC-MELG. When melanocytes and melanoma cells were treated with a potent IFN inducer, polyinosinic:polycytidylic acid (poly I:C), the mRNA expression of both IFN-alpha and IFN-beta was significantly upregulated. Poly I:C was not able to induce melanocytes or melanoma cells to produce detectable amounts of IFN-alpha protein, but able to induce a significant amount of IFN-beta in melanocytes and two of the melanoma cell lines: MMAc and VMRC-MELG. Moreover, similar to exogenous IFN-alpha and IFN-beta, poly I:C significantly inhibited the proliferation of all five melanoma cell lines. This suppressive effect was partially blocked by anti-IFN-beta antibody treatment in the IFN-beta-producing melanoma cell lines: MMAc and VMRC-MELG, but not in the non-IFN-beta-producing cell lines: G-361, C32TG and MEWO. Collectively, these studies have demonstrated for the first time that human melanocytes and melanoma cells produce IFN-beta. Furthermore, melanoma cells are capable of suppressing their own proliferation via secretion of endogenous IFN-beta. This finding may have important implications for melanoma therapy.
干扰素（IFN）-α和IFN-β已被用作细胞因子疗法用于治疗黑色素瘤。虽然先前的研究表明黑素细胞和黑色素瘤细胞会产生多种细胞因子，但黑素细胞和黑色素瘤细胞本身是否产生IFN-α或IFN-β仍不清楚。在本研究中，我们在mRNA和蛋白质水平上研究了人黑素细胞以及五种黑色素瘤细胞系：G-361、C32TG、MMAc、MEWO和VMRC-MELG中IFN-α或IFN-β的表达。在正常人黑素细胞中检测到了IFN-α和IFN-β mRNA。同样，在所有五种黑色素瘤细胞系中都检测到了IFN-α mRNA。然而，仅在一种黑色素瘤细胞系VMRC-MELG中检测到了IFN-β mRNA。当用强效IFN诱导剂聚肌苷酸：聚胞苷酸（poly I:C）处理黑素细胞和黑色素瘤细胞时，IFN-α和IFN-β的mRNA表达均显著上调。Poly I:C不能诱导黑素细胞或黑色素瘤细胞产生可检测量的IFN-α蛋白，但能够在黑素细胞和两种黑色素瘤细胞系MMAc和VMRC-MELG中诱导产生大量的IFN-β。此外，与外源性IFN-α和IFN-β相似，poly I:C显著抑制了所有五种黑色素瘤细胞系的增殖。在产生IFN-β的黑色素瘤细胞系MMAc和VMRC-MELG中，抗IFN-β抗体处理部分阻断了这种抑制作用，但在不产生IFN-β的细胞系G-361、C32TG和MEWO中则没有。总体而言，这些研究首次证明人黑素细胞和黑色素瘤细胞可产生IFN-β。此外，黑色素瘤细胞能够通过分泌内源性IFN-β来抑制自身增殖。这一发现可能对黑色素瘤治疗具有重要意义。
