Abstract:
: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.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Yoshida K,Kondoh A,Narumi K,Yoshida T,Aoki Kdoi
10.1016/j.bbrc.2008.08.132subject
Has Abstractpub_date
2008-11-14 00:00:00pages
299-304issue
2eissn
0006-291Xissn
1090-2104pii
S0006-291X(08)01682-3journal_volume
376pub_type
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