A synthetic peptide inhibitor for alpha-chemokines inhibits the tumour growth and pulmonary metastasis of human melanoma cells in nude mice

Growth-related oncogene-alpha (GRO alpha) was first described as an autocri ne mitogen and growth factor for melanoma cells. More recent studies show t hat GRO alpha, interleukin-8 (IL-8) and other members of the alpha-chemokin e superfamily are also angiogenic. Therefore, we sought to determine if inh ibitors of the alpha-chemokine receptor would be effective in inhibiting th e tumour growth and pulmonary metastasis of human melanoma cells. We determ ined that melanocytes and 12 human melanoma cell lines produce both GRO alp ha and IL-8. The proliferation of A375SM, a highly metastatic cell line, an d C8161-C were significantly increased by human recombinant GRO alpha and i nhibited by anti-human GRO alpha monoclonal antibody. Antileukinate, a pote nt inhibitor of alpha-chemokine receptor binding, inhibited the binding of GRO alpha to its receptors in melanocytes and all 12 melanoma cell lines te sted. Antileukinate also suppressed proliferation of A375SM and C8161-C cel ls in a dose-dependent manner, and the suppression was not due to cytotoxic effects. Furthermore, continuous administration of antileukinate inhibited the tumour growth and pulmonary metastasis of A375SM cells in athymic BALB /c nude mice. These findings suggest that antileukinate inhibits the growth of melanoma cells by preventing GRO alpha from binding to its receptors. T his suggests a possible use of alpha-chemokine receptor inhibitors such as antileukinate in the treatment of malignant melanoma. (C) 1999 Lippincott W illiams & Wilkins.