A synthetic peptide inhibitor for α-chemokines inhibits the growth of melanoma cell lines

Abstract

Melanoma growth stimulatory activity (MGSA/GROα) is a 73 amino acid peptide sharing sequence characteristics with the α-chemokine superfamily. MGSA/GROα is produced by diverse melanoma cell lines and reported to act as an autocrine growth factor for the cells. We tested the binding of MGSA/GROα to melanoma cell lines, Hs 294T and RPMI-7951, and found that these cells could bind to MGSA/GROα but not to interleukin-8. Recently, we defined a novel hexapeptide, antileukinate, which is a potent inhibitor of binding of α-chemokines to their receptors on neutrophils. When antileukinate was added to melanoma cells, it inhibited the binding of MGSA/GROα. The growth of cells from both melanoma cell lines was suppressed completely in the presence of 100 μM peptide. The cell growth inhibition was reversed by the removal of the peptide from the culture media or by the addition of the excess amount of MGSA/GROα. The viability of Hs 294T cells in the presence of 100 μM peptide was > 92%. These findings suggest that MGSA/GROα is an essential autostimulatory growth factor for melanoma cells and antileukinate inhibits their growth by preventing MGSA/GROα from binding to its receptors.