A SYNTHETIC PEPTIDE INHIBITOR FOR ALPHA-CHEMOKINES INHIBITS THE GROWTH OF MELANOMA CELL-LINES

Melanoma growth stimulatory activity (MGSA/GRO alpha is a 73 amino aci d peptide sharing sequence characteristics with the alpha-chemokine su perfamily. MGSA/GRO alpha is produced by diverse melanoma cell lines a nd reported to act as an autocrine growth factor for the cells. We tes ted the binding of MGSA/GRO alpha to melanoma cell lines, Hs 294T and RPMI-7951, and found that these cells could bind to MGSA/GRO alpha but not to interleukin-8. Recently, we defined a novel hexapeptide, antil eukinate, which is a potent inhibitor of binding of alpha-chemokines t o their receptors on neutrophils. When antileukinate was added to mela noma cells, it inhibited the binding of MGSA/GRO alpha. The growth of cells from both melanoma cell lines was suppressed completely in the p resence of 100 mu M peptide, The cell growth inhibition was reversed b y the removal of the peptide from the culture media or by the addition of the excess amount of MGSA/GRO alpha, The viability of Hs 294T cell s in the presence of 100 mu M peptide was > 92%. These findings sugges t that MGSA/GRO alpha is an essential autostimulatory growth factor fo r melanoma cells and antileukinate inhibits their growth by preventing MGSA/GRO alpha. from binding to its receptors.