A C5 Fragment with Chemotactic Activity for Tumor Cells

Abstract The chemotactic behavior of several animal tumor cells (Novikoff hepatoma cells, Walker carcinosarcoma cells, and murine mastocytoma cells) was studied in modified Boyden chambers. Leukotactic factors derived from complement (C3 and C5 fragments) or from bacteria (Escherichia coli) had no chemotactic activity for tumor cells. Incubation of normal rat or human serum with a crude extract from Walker tumor cells resulted in the generation of a factor chemotactic for tumor cells but not for leukocytes. Experiments using complement deficient (acquired or genetic) serum, complement-specific antiserums, and preparations of purified complement components indicated that the factor chemotactic for tumor cells was a fragment of the fifth component of complement (C5) produced by a C5-cleaving enzyme extractable from tumor cells. Sucrose density gradient analysis and Sephadex gel filtration chromatography indicated that the C5 fragment chemotactic for tumor cells had physicochemical features different from the C5 fragment chemotactically active for neutrophils. When the trypsin-produced C5 fragments with chemotactic activity for neutrophils were chromatographically isolated, further treatment with the C5-cleaving enzyme from tumor cells resulted in the disappearance of chemotactic activity for neutrophils and the appearance of chemotactic activity for tumor cells, suggesting that the tumor cell chemotactic factor may derive from a larger fragment containing chemotactic activity for neutrophils. These data indicate that the complement system may influence the migrational behavior of tumor cells. (Supported by NCI Grant CA 17665 from the NIH and by the Andres Soriano Cancer Research Fund.)