Extracellular matrix interacts with interferon α protein: Retention and display of cytotoxicity

Abstract

We have been investigating the efficacy of an intratumoral interferon (IFN)-α gene transfer against solid cancers, and found that when the gene is transduced into the subcutaneous tumors, IFN-α concentration is markedly increased in the injected tumor but not in the serum. To explain this effective confinement of IFN-α to target tissues, we hypothesized that the extracellular matrix in the tumors interacts with IFN-α. In this study, a solid-phase-binding assay and immunoprecipitation demonstrated that the IFN-α binds directly to matrix proteins. Immunohistochemical staining showed a co-localization of IFN-α with pericellular fibronectin. In addition, matrix-bound IFN-α protein transduced intracellular signaling and potentiated its cytotoxic activity, suggesting that the retention of IFN-α 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-α gene transfer over the conventional parenteral therapy both in the safety and efficacy.