Interferons alpha and beta down-regulate the expression of basic fibroblast growth factor in human carcinomas

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.