Neuropeptide regulation of cell-mediated cytotoxicity against human tumor cells

The effects of the brain-gastrointestinal polypeptide neurotransmitters bombesin, substance P, neurotensin, and somatostatin-14 on cytotoxicity of peripheral blood mononuclear cells against K-562 and CaCo-2 tumour cells were investigated. Bombesin significantly stimulated cytotoxicity against CaCo-2 target cells (10(-12), 10(-10) M and 10(-6) M) and against K-562 target cells (10(-12) and 10(-10) M) in the short 4 hour assay. Substance P showed a tendency to stimulate cytotoxicity at higher concentrations but the changes observed did not reach significance because of large inter-individual variation of responsiveness. Neurotensin did not influence cytotoxicity against either target cell lines. Somatostatin was found to have no influence on cytotoxicity of peripheral blood mononuclear cells but was the only peptide tested which markedly increased chromium release by target cells alone. These findings support the idea that brain-gastrointestinal neuropeptides can play a part in tumour cytotoxicity.