Stimulation of rat peritoneal mast cell migration by tumor-derived peptides

The accumulation of mast cells is characteristic of a number of pathological states. We demonstrate here the directional motility of mast cells in vitro in response to tumor-derived peptides. Rat peritoneal mast cells were isolated on Percoll gradients and maintained in serum-free medium containing transferrin, albumin, soybean lipid, and cholesterol. The isolated mast cells migrated under agarose in response to medium conditioned by any of eight tumor cell lines but not to medium conditioned by any of a variety of nontumorigenic cell types. The tumor-derived activity is dialyzable (cutoff, Mr 3500), stable to trypsin treatment and to heating at 56 degrees, but destroyed by heating to 100 degrees or by treatment with Streptomyces griseus protease or carboxypeptidase A. Ultrafiltration suggests a molecular weight of 300 to 1000. Two tripeptides, glycylhistidyllysine and N-formylmethionylleucylphenylalanine, were also found to be potent chemoattractants for mast cells. N-Formylmethionylphenylalanine and valylglycylserylglutamic acid (eosinophil chemotactic Factor A) had significantly less chemoattractant activity over the same range of concentrations. Several peptide analogues of glycylhistidyllysine were tested and found to have no activity. The growth of capillary blood vessels toward a growing tumor is generally preceded by an accumulation of mast cells at the tumor site. Based on the results presented here and previous data from our laboratory on mast cell stimulation of capillary endothelial cell migration, we propose an hypothesis that the chemoattraction of mast cells by tumor-derived peptides may be an important early event in tumor neovascularization.