Retroviral gene transfer of interferon-inducible protein 10 inhibits growth of human melanoma xenografts

Andrew L. Feldman, Josef Friedl, Titia E. Lans, Steven K. Libutti, Dominique Lorang, Marshall S. Miller, Ewa M. Turner, Stephen M. Hewitt, H. Richard Alexander

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Interferon-inducible protein 10 (IP-10) is an immunomodulatory chemokine recently recognized to have potent antiangiogenic activity in vivo. Due to difficulties in the stability, manufacture and chronic administration of recombinant forms of endogenous antiangiogenic proteins, antiangiogenic gene therapy has emerged as a promising new form of cancer treatment. We retrovirally transduced A375 human melanoma cells with the human IP-10 gene and injected cells subcutaneously into nude mice. IP-10-transduced cells also were mixed with null-transduced cells in varying proportions before injection. In vivo growth of IP-10-transduced melanoma cells was markedly diminished compared to parental or null-transduced cells (p = 0.0002, Kruskal-Wallis test). This growth inhibition was associated with a marked reduction in microvessel density. The degree of growth inhibition of tumors following injection of a mixed population of null-and IP-10-transduced cells was directly associated with the fraction of IP-10-transduced cells present. We conclude that retroviral transduction of human melanoma cells with the IP-10 gene leads to sufficient protein secretion to inhibit angiogenesis and tumor growth. These findings suggest that IP-10 gene therapy might be an effective therapy in patients with cancer. Published 2002 Wiley-Liss, Inc.

Original languageEnglish (US)
Pages (from-to)149-153
Number of pages5
JournalInternational Journal of Cancer
Volume99
Issue number1
DOIs
StatePublished - May 1 2002
Externally publishedYes

Fingerprint

Chemokine CXCL10
Heterografts
Melanoma
Growth
Genes
Proteins
Null Lymphocytes
Genetic Therapy
Neoplasms
Injections
Microvessels
Chemokines
Nude Mice

Keywords

  • Angiogenesis
  • Cancer
  • Chemokine
  • Endothelium
  • Gene therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Feldman, A. L., Friedl, J., Lans, T. E., Libutti, S. K., Lorang, D., Miller, M. S., ... Alexander, H. R. (2002). Retroviral gene transfer of interferon-inducible protein 10 inhibits growth of human melanoma xenografts. International Journal of Cancer, 99(1), 149-153. https://doi.org/10.1002/ijc.10292

Retroviral gene transfer of interferon-inducible protein 10 inhibits growth of human melanoma xenografts. / Feldman, Andrew L.; Friedl, Josef; Lans, Titia E.; Libutti, Steven K.; Lorang, Dominique; Miller, Marshall S.; Turner, Ewa M.; Hewitt, Stephen M.; Alexander, H. Richard.

In: International Journal of Cancer, Vol. 99, No. 1, 01.05.2002, p. 149-153.

Research output: Contribution to journalArticle

Feldman, AL, Friedl, J, Lans, TE, Libutti, SK, Lorang, D, Miller, MS, Turner, EM, Hewitt, SM & Alexander, HR 2002, 'Retroviral gene transfer of interferon-inducible protein 10 inhibits growth of human melanoma xenografts', International Journal of Cancer, vol. 99, no. 1, pp. 149-153. https://doi.org/10.1002/ijc.10292
Feldman, Andrew L. ; Friedl, Josef ; Lans, Titia E. ; Libutti, Steven K. ; Lorang, Dominique ; Miller, Marshall S. ; Turner, Ewa M. ; Hewitt, Stephen M. ; Alexander, H. Richard. / Retroviral gene transfer of interferon-inducible protein 10 inhibits growth of human melanoma xenografts. In: International Journal of Cancer. 2002 ; Vol. 99, No. 1. pp. 149-153.
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