TGF-α antisense gene therapy inhibits head and neck squamous cell carcinoma growth in vivo

S. Endo, Q. Zeng, N. A. Burke, Yukai He, M. F. Melhem, S. F. Watkins, M. N. Lango, S. D. Drenning, L. Huang, J. Rubin Grandis

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Unlike normal mucosal squamous epithelial cells, head and neck squamous cell carcinomas (HNSCCs) overexpress TGF-α mRNA and protein which is required to sustain the proliferation of HNSCC cells in vitro. To determine whether TGF-α expression contributes to tumor growth in vivo, cationic liposome-mediated gene transfer was used to deliver an antisense expression construct targeting the human TGF-α gene into human head and neck tumor cells, grown as subcutaneous xenografts in nude mice. The TGF-α anti-sense gene was immediately detected in the cytoplasm of the tumor cells, translocated to the nucleus by 12 h and remained localized to the nucleus for up to 3 days. Direct inoculation of the TGF-α antisense (but not the corresponding sense) construct into established HNSCC tumors resulted in inhibition of tumor growth. Sustained antitumor effects were observed for up to 1 year after the treatments were discontinued. Down-modulation of TGF-α was accompanied by increased apoptosis in vivo. These experiments indicate that interference with the TGF-α/EGFR autocrine signaling pathway may be an effective therapeutic strategy for cancers which overexpress this ligand/receptor pair.

Original languageEnglish (US)
Pages (from-to)1906-1914
Number of pages9
JournalGene Therapy
Volume7
Issue number22
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

Fingerprint

Genetic Therapy
Growth
Neoplasms
Autocrine Communication
Genes
Heterografts
Nude Mice
Liposomes
Carcinoma, squamous cell of head and neck
Cytoplasm
Neck
Epithelial Cells
Head
Apoptosis
Ligands
Messenger RNA
Therapeutics
Proteins

Keywords

  • Head and neck cancer
  • Transforming growth factor alpha

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Endo, S., Zeng, Q., Burke, N. A., He, Y., Melhem, M. F., Watkins, S. F., ... Rubin Grandis, J. (2000). TGF-α antisense gene therapy inhibits head and neck squamous cell carcinoma growth in vivo. Gene Therapy, 7(22), 1906-1914. https://doi.org/10.1038/sj.gt.3301315

TGF-α antisense gene therapy inhibits head and neck squamous cell carcinoma growth in vivo. / Endo, S.; Zeng, Q.; Burke, N. A.; He, Yukai; Melhem, M. F.; Watkins, S. F.; Lango, M. N.; Drenning, S. D.; Huang, L.; Rubin Grandis, J.

In: Gene Therapy, Vol. 7, No. 22, 01.01.2000, p. 1906-1914.

Research output: Contribution to journalArticle

Endo, S, Zeng, Q, Burke, NA, He, Y, Melhem, MF, Watkins, SF, Lango, MN, Drenning, SD, Huang, L & Rubin Grandis, J 2000, 'TGF-α antisense gene therapy inhibits head and neck squamous cell carcinoma growth in vivo', Gene Therapy, vol. 7, no. 22, pp. 1906-1914. https://doi.org/10.1038/sj.gt.3301315
Endo, S. ; Zeng, Q. ; Burke, N. A. ; He, Yukai ; Melhem, M. F. ; Watkins, S. F. ; Lango, M. N. ; Drenning, S. D. ; Huang, L. ; Rubin Grandis, J. / TGF-α antisense gene therapy inhibits head and neck squamous cell carcinoma growth in vivo. In: Gene Therapy. 2000 ; Vol. 7, No. 22. pp. 1906-1914.
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