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

Abstract

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.

• Authors: Kotaro Hirai, Hideo Sasaki, Hiromi Sakamoto, Fumitaka Takeshita, Koji Asano, Yoshinobu Kubota, Takahiro Ochiya, Masaaki Terada
• Journal: The journal of gene medicine (J Gene Med) Vol. 5 Issue 11 Pg. 951-7 (Nov 2003) ISSN: 1099-498X [Print] England
• PMID: 14601132 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2003 John Wiley & Sons, Ltd.

Chemical References

• DNA Primers
• FGF4 protein, human
• Fgf4 protein, mouse
• Fibroblast Growth Factor 4
• Oligodeoxyribonucleotides, Antisense
• Proto-Oncogene Proteins
• atelocollagen
• Fibroblast Growth Factors
• Collagen

Topics

• Animals
• Cell Line, Tumor
• Collagen (metabolism)
• DNA Primers
• Enzyme-Linked Immunosorbent Assay
• Fibroblast Growth Factor 4
• Fibroblast Growth Factors (drug effects, metabolism)
• Gene Expression Regulation, Neoplastic
• Germinoma (metabolism)
• Humans
• Male
• Mice
• Mice, Nude
• Oligodeoxyribonucleotides, Antisense (metabolism, pharmacology)
• Proto-Oncogene Proteins (drug effects, metabolism)
• Testicular Neoplasms (metabolism)
• Transfection