Identification and partial characterization of a low-molecular-weight inhibitor of leukotaxis from fibrosarcoma cells.

Lysate from T-241 murine fibrosarcoma cells contains a low-molecular-weight (Mr less than 1000), heat-stable peptide factor which has antichemotactic activity for both macrophages and polymorphonuclear leukocytes in vitro. The tumor factor was partially purified from an alcohol extract of the fibrosarcomas by gel filtration, anion exchange chromatography, and paper chromatography successively. This factor inhibits both the hydrolytic cleavage of the peptide attractant N-formylmethionylleucylphenylalanine by polymorphonuclear leukocytes and the methylation of both protein carboxyl groups and membrane phospholipids. Furthermore, the factor does not appear to compete with N-formylmethionylleucylphenylalanine for its receptor. The tumor-derived material, therefore, affects biochemical reactions believed to have roles in the expression of an adequate leukotactic response. These data suggest that depressed inflammatory responses at sites of neoplasms may result in part from release of small, potent inhibitors of leukotaxis from tumors themselves.