STIMULATION OF RAT PERITONEAL MAST-CELL MIGRATION BY TUMOR-DERIVED PEPTIDES

  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (12) , 5857-5861
Abstract
The accumulation of mast cells is characteristic of a number of pathological states. The directional motility of mast cells in vitro in response to tumor-derived peptides is demonstrated. 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 8 tumor cells lines but not to medium conditioned by any of a variety of nontumorigenic cell types. The tumor-derived activity is dialyzable (cutoff, MW 3500), stable to trypsin treatment and to heating at 56.degree., but destroyed by heating to 100.degree. or by treatment with Streptomyces griseus protease or carboxypeptidase A. Ultrafiltration suggests a MW 300-1000. Two tripeptides, glycylhistidyllysine and N-formylmethionylleucylphenylalanine, were also 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 analogs of glycylhistidyllysine were tested and had 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 laboratory on mast cell stimulation of capillary endothelial cell migration, the chemoattraction of mast cells by tumor-derived peptides may be an important early event in tumor neovascularization.