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Interferons alpha and beta down-regulate the expression of basic fibroblast growth factor in human carcinomas
R K Singh1, M Gutman, C D Bucana
1Department of Cell Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Abstract:
We investigated the influence of interferons alpha, beta, and gamma (IFN-alpha, -beta, and -gamma) on the production of basic fibroblast growth factor (bFGF) by human renal carcinoma cells. The human renal carcinoma cell metastatic line SN12PM6 was established in culture from a lung metastasis and SN12PM6-resistant cells were selected in vitro for resistance to the antiproliferative effects of IFN-alpha or IFN-beta. IFN-alpha and IFN-beta, but not IFN-gamma, down-regulated the expression of bFGF at the mRNA and protein levels by a mechanism independent of their antiproliferative effects. Down-regulation of bFGF required a long exposure (> 4 days) of cells to low concentrations (> 10 units/ml) of IFN-alpha or IFN-beta. The withdrawal of IFN-alpha or IFN-beta from the medium permitted SN12PM6-resistant cells to resume production of bFGF. The incubation of human bladder, prostate, colon, and breast carcinoma cells with noncytostatic concentrations of IFN-alpha or IFN-beta also produced down-regulation of bFGF production.
Insights
Interferons alpha and beta, but not gamma, reduce basic fibroblast growth factor (bFGF) production in various cancer cells. This effect is independent of their antiproliferative action and requires prolonged exposure.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Basic fibroblast growth factor (bFGF) plays a role in tumor growth and metastasis.
- Interferons (IFNs) are cytokines with diverse biological activities, including anti-cancer effects.
Purpose of the Study:
- To investigate the impact of interferons alpha, beta, and gamma on bFGF production in human renal carcinoma cells.
- To determine if IFN-induced down-regulation of bFGF is linked to their antiproliferative effects.
Main Methods:
- Established and utilized a human renal carcinoma cell line (SN12PM6) and derived IFN-resistant variants.
- Quantified bFGF mRNA and protein levels following treatment with IFN-alpha, -beta, and -gamma.
- Exposed various human carcinoma cell lines (bladder, prostate, colon, breast) to IFNs.
Main Results:
- IFN-alpha and IFN-beta significantly down-regulated bFGF expression at both mRNA and protein levels in SN12PM6 cells.
- IFN-gamma did not affect bFGF production.
- Down-regulation of bFGF by IFN-alpha and IFN-beta was concentration- and time-dependent, occurring with prolonged exposure to low concentrations and independent of antiproliferative effects.
- bFGF production resumed upon withdrawal of IFN-alpha or IFN-beta.
- Noncytostatic concentrations of IFN-alpha and IFN-beta also reduced bFGF production in bladder, prostate, colon, and breast carcinoma cells.
Conclusions:
- IFN-alpha and IFN-beta suppress bFGF production in renal carcinoma cells through a mechanism distinct from their antiproliferative activity.
- This suppressive effect on bFGF is observed across multiple human carcinoma cell types.
- Targeting bFGF production with interferons may represent a therapeutic strategy in various cancers.