Extracellular matrix interacts with interferon {alpha} protein: Retention and display of cytotoxicity

We have been investigating the efficacy of an intratumoral interferon (IFN)-{alpha} gene transfer against solid cancers, and found that when the gene is transduced into the subcutaneous tumors, IFN-{alpha} concentration is markedly increased in the injected tumor but not in the serum. To explain thi...

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Bibliographic Details
Published inBiochemical and biophysical research communications Vol. 376; no. 2
Main Authors Yoshida, Kimiko, Kondoh, Atsushi, Narumi, Kenta, Yoshida, Teruhiko, Aoki, Kazunori
Format Journal Article
LanguageEnglish
Published United States 14.11.2008
Subjects
60 APPLIED LIFE SCIENCES
GENES
INTERFERON
NEOPLASMS
THERAPY
TOXICITY
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Summary:We have been investigating the efficacy of an intratumoral interferon (IFN)-{alpha} gene transfer against solid cancers, and found that when the gene is transduced into the subcutaneous tumors, IFN-{alpha} concentration is markedly increased in the injected tumor but not in the serum. To explain this effective confinement of IFN-{alpha} to target tissues, we hypothesized that the extracellular matrix in the tumors interacts with IFN-{alpha}. In this study, a solid-phase-binding assay and immunoprecipitation demonstrated that the IFN-{alpha} binds directly to matrix proteins. Immunohistochemical staining showed a co-localization of IFN-{alpha} with pericellular fibronectin. In addition, matrix-bound IFN-{alpha} protein transduced intracellular signaling and potentiated its cytotoxic activity, suggesting that the retention of IFN-{alpha} protein on extracellular matrix is likely to play a role in its in vivo biological activity. The data suggest a therapeutic advantage of the intratumoral IFN-{alpha} gene transfer over the conventional parenteral therapy both in the safety and efficacy.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2008.08.132