Abstract
We investigated the effects of human recombinant interferons (r-IFNs) on gelatinase production and invasion by human renal-cell carcinoma (HRCC). Incubation of KG-2 HRCC with human r-IFN-beta or -gamma (but not -alpha) suppressed transcription of the 72-kDa gelatinase gene and, hence, production of gelatinase activity. These inhibitory effects of interferons (IFNs) were independent of their antiproliferative effects. Treatment of KG-2 cell with r-IFN-beta or -gamma significantly inhibited cell invasion through reconstituted basement membrane toward chemoattractants produced by kidney fibroblasts. The inhibitory activity of r-IFNs was specific to the KG-2 cells since gelatinase activity by various fibroblasts was unaffected. These findings suggest that r-IFN-beta or IFN-gamma may be used to inhibit the invasive potential of HRCC.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Carcinoma, Renal Cell / drug therapy
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Carcinoma, Renal Cell / enzymology*
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Carcinoma, Renal Cell / pathology*
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Collagen / metabolism
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Fibroblasts / drug effects
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Fibroblasts / enzymology
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Gelatinases / antagonists & inhibitors
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Gelatinases / biosynthesis*
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Gelatinases / genetics
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Humans
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Interferon Type I / pharmacology
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Interferon beta-1a
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Interferon beta-1b
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Interferon-beta / pharmacology*
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Interferon-gamma / pharmacology*
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Kidney / cytology
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Kidney / drug effects
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Kidney / enzymology
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Kidney Neoplasms / drug therapy
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Kidney Neoplasms / enzymology*
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Kidney Neoplasms / pathology*
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Neoplasm Invasiveness
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Recombinant Proteins
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Skin / cytology
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Skin / drug effects
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Skin / enzymology
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Tumor Cells, Cultured / drug effects
Substances
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Interferon Type I
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RNA, Messenger
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Recombinant Proteins
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Interferon beta-1b
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Interferon-beta
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Interferon-gamma
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Collagen
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Gelatinases
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Interferon beta-1a