Antisense oligodeoxynucleotide against HST-1/FGF-4 suppresses tumorigenicity of an orthotopic model for human germ cell tumor in nude mice.
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.


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.
Section for Studies on Metastasis, National Cancer Center Research Institute, 1-1, Tsukiji, 5-chome, Chuo-ku, Tokyo 104-0045, Japan.
Kotaro
K
Hirai
Hideo
H
Sasaki
Hiromi
H
Sakamoto
Fumitaka
F
Takeshita
Koji
K
Asano
Yoshinobu
Y
Kubota
Takahiro
T
Ochiya
Masaaki
M
Terada
D000818:Animals; D045744:Cell Line, Tumor; D003094:Collagen / Q000378:metabolism; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000187:drug effects* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D018237:Germinoma / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D020319:Oligodeoxyribonucleotides, Antisense / Q000378:metabolism / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000187:drug effects* / Q000378:metabolism; D013736:Testicular Neoplasms / Q000378:metabolism*; D014162:Transfection
D017931:DNA Primers; C496445:FGF4 protein, human; C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; D020319:Oligodeoxyribonucleotides, Antisense; D011518:Proto-Oncogene Proteins; C059821:atelocollagen; D005346:Fibroblast Growth Factors; D003094:Collagen