Interferon-alpha-induced inhibition of B16 melanoma cell proliferation: Interference with the bFGF autocrine growth circuit

The molecular mechanisms underlying the growth inhibition induced by interf eron-alpha (IFN-alpha) in B16 murine melanoma cells were investigated, IFN- alpha did not induce cell apoptosis, but strongly interfered with the synth esis of basic fibroblast growth factor (bFGF), which acts as an autocrine g rowth factor in this system. Inhibition of bFGF synthesis was observed at t he same concentrations (50-500 pM, 10-100 U/ml) of IFN-alpha able to induce growth arrest of B16 melanoma cells. Although the synthesis of acidic (a)F GF was only slightly affected by IFN-alpha, the cytokine induced release of an aFGF-related low-molecular-weight peptide, which was able to interfere with bFGF binding to surface receptors, Thus, the molecular mechanisms of I FN-alpha activity on melanoma cells include a specific modulation of the bF GF autocrine circuit. (C) 1999 Academic Press.