BACKGROUND: Overexpression of the fibroblast growth factor HST-1/FGF-4 gene is thought to mediate growth properties and malignancy in human testicular germ cell tumors. We have studied the effect that an antisense oligodeoxynucleotide against HST-1/FGF-4 suppresses tumorigenicity of a human germ cell tumor. METHODS AND RESULTS: To test whether HST-1/FGF-4 could be the target of gene therapy for testicular carcinoma, 20-mer phosphorothioate oligodeoxynucleotides (ODNs) directed against human HST-1/FGF-4 were analyzed for their antitumor activity. The antisense HST-1/FGF-4 ODNs suppressed HST-1/FGF-4 production by NEC8 human nonseminomatous germ cells and inhibited their cell growth in vitro. Furthermore, after orthotopic implantation of NEC8 cells, combined treatment with antisense HST-1/FGF-4 ODNs and Atelocollagen significantly inhibited the growth of testicular tumors as well as the incidence of lymph node metastasis. In contrast, administration of antisense ODNs alone was less effective. CONCLUSIONS: Collectively, these results indicate that the antisense method against HST-1/FGF-4 gene expression will be a novel therapeutic approach for male germ cell tumors. The use of Atelocollagen-mediated administration of the antisense HST-1/FGF-4 ODNs may be useful in enhancing the effects of antisense therapy. Copyright 2003 John Wiley & Sons, Ltd.
BACKGROUND: Overexpression of the fibroblast growth factor HST-1/FGF-4 gene is thought to mediate growth properties and malignancy in human testicular germ cell tumors. We have studied the effect that an antisense oligodeoxynucleotide against HST-1/FGF-4 suppresses tumorigenicity of a human germ cell tumor. METHODS AND RESULTS: To test whether HST-1/FGF-4 could be the target of gene therapy for testicular carcinoma, 20-mer phosphorothioate oligodeoxynucleotides (ODNs) directed against humanHST-1/FGF-4 were analyzed for their antitumor activity. The antisense HST-1/FGF-4 ODNs suppressed HST-1/FGF-4 production by NEC8 human nonseminomatous germ cells and inhibited their cell growth in vitro. Furthermore, after orthotopic implantation of NEC8 cells, combined treatment with antisense HST-1/FGF-4 ODNs and Atelocollagen significantly inhibited the growth of testicular tumors as well as the incidence of lymph node metastasis. In contrast, administration of antisense ODNs alone was less effective. CONCLUSIONS: Collectively, these results indicate that the antisense method against HST-1/FGF-4 gene expression will be a novel therapeutic approach for male germ cell tumors. The use of Atelocollagen-mediated administration of the antisense HST-1/FGF-4 ODNs may be useful in enhancing the effects of antisense therapy. Copyright 2003 John Wiley & Sons, Ltd.